Trial Files Throwback Thursday: Sodium Bicarbonate for CKD, ASA+DOAC for PAD, Anti-Fibrotics for IPF
What’s the rationale for giving sodium bicarbonate to patients with CKD and metabolic acidosis?
Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status
de Brito-Ashurst I et al. JASN (September 2009)
Bottom line: This randomized controlled trial evaluated the effect of oral sodium bicarbonate supplementation on renal function and nutritional status in 134 adult patients with chronic kidney disease (CKD), defined as creatinine clearance (CrCl) of 15-30 mL/min per 1.73 m2, and serum bicarbonate levels of 16-20 mmol/L. The intervention group received oral bicarbonate supplementation while the control group received standard care for 2 years. The primary outcomes were rate of decline in CrCl, proportion of patients with rapid decline in CrCl (>3 mL/min per per 1.73 m2/yr), and development of end-stage renal disease (ESRD) (CrCl < 10 mL/min). Secondary endpoints were dietary protein intake, normalized protein nitrogen appearance, serum albumin, and mid-arm muscle circumference. The results showed that bicarbonate supplementation significantly slowed the rate of decline in CrCl compared to standard care (5.93 versus 1.88 ml/min 1.73 m2; P < 0.0001) and reduced the risk of rapid progression (9 versus 45%; relative risk 0.15; 95% confidence interval 0.06 to 0.40; P < 0.0001) and ESRD (6.5 versus 33%; relative risk 0.13; 95% confidence interval 0.04 to 0.40; P < 0.001) compared to standard care. Nutritional parameters also improved with supplementation, which was was well tolerated. In conclusion, this study demonstrates the benefit of bicarbonate supplementation in slowing the progression of renal failure and improving nutritional status in patients with CKD.
Why should I consider low-dose rivaroxaban in addition to ASA for patients with stable cardiovascular disease?
Rivaroxaban with or without Aspirin in Stable Cardiovascular Disease (COMPASS)
Eikelboom J et al. NEJM (October 2017)
Bottom Line: This double-blind trial evaluated the effectiveness of rivaroxaban alone or in combination with aspirin for secondary cardiovascular prevention in patients with stable atherosclerotic vascular disease. The study included 27,395 participants who were randomly assigned to receive either rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily), rivaroxaban alone (5 mg twice daily), or aspirin alone (100 mg once daily). The primary outcome was a composite of cardiovascular death, stroke, or myocardial infarction at a mean follow-up of 23 months. The results showed that the rivaroxaban-plus-aspirin group had significantly lower rates of primary outcome compared to the aspirin-alone group (379 patients [4.1%] vs. 496 patients [5.4%]; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.86; P<0.001; z=−4.126), but also had a higher risk of major bleeding events (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001). There was no significant difference in intracranial or fatal bleeding between the two groups. The rivaroxaban-alone group did not show better cardiovascular outcomes compared to the aspirin-alone group, but had a higher risk of major bleeding events. Overall, rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) was found to be more effective for secondary cardiovascular prevention in this patient population.
What’s the evidence for prescribing nintedanib for patients with IPF?
Efficacy and Safety of Nintedanib in Idiopathic Pulmonary Fibrosis (INPULSIS)
Richeldi L et al. NEJM (May 2014)
Bottom Line: This phase 3, double-blind, randomized trial evaluated the efficacy and safety of 150 mg of nintedanib, an intracellular inhibitor, twice daily compared to placebo in patients with idiopathic pulmonary fibrosis (IPF). A total of 1066 patients were included in two replicate 52-week trials (INPULSIS-1 and INPULSIS-2) and the primary outcome was the annual rate of decline in forced vital capacity (FVC). Key secondary end points included time to first acute exacerbation and change from baseline in the total score on the St. George’s Respiratory Questionnaire, both assessed over a 52 week period. The results showed a significant reduction in FVC decline with nintedanib compared to placebo. FVC decline was -114.7 mL with nintedanib versus -239.9 mL with placebo in INPULSIS-1 (difference, 125.3 ml; 95% confidence interval [CI], 77.7 to 172.8; P<0.001) and -113.6 versus -207.3 in INPULSIS-2 (difference, 93.7 ml; 95% CI, 44.8 to 142.7; P<0.001). INPULSIS-1 showed no significant difference in time to first acute exacerbation between nintedanib and placebo (hazard ratio with nintedanib, 1.15; 95% CI, 0.54 to 2.42; P=0.67), whereas with INPULSIS-2, there was a significant benefit seen with nintedanib (hazard ratio, 0.38; 95% CI, 0.19 to 0.77; P=0.005). The most common adverse event was diarrhea, leading to discontinuation of the study medication in less than 5% of patients. In conclusion, nintedanib was effective in slowing disease progression in patients with idiopathic pulmonary fibrosis and was well tolerated.
Trial Files Issue #2024-19
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