Trial Files Throwback Thursday: ACEi for Diabetic Nephropathy, Antiplts for PAD, Bisphosphonates for Bony Mets
Why is ACE inhibition recommended for patients with diabetic nephropathy?
The Effect of Angiotensin-Converting-Enzyme Inhibition on Diabetic Nephropathy
Lewis E et al. NEJM (November 1993)
Bottom line: This randomized, controlled trial compared the effects of captopril versus placebo in patients with insulin-dependent diabetes mellitus, urinary protein excretion ≥ 500 mg/day, and serum creatinine concentration ≤ 2.5 mg/dL. The study aimed to determine whether captopril has renal-protective properties independent of its effect on blood pressure in diabetic nephropathy. Eligible patients were required to have systolic blood pressure below 140 mm Hg and diastolic blood pressure below 90 mm Hg without the use of ACE inhibitors or calcium agonists. The primary outcome was a doubling of baseline serum creatinine concentration, which occurred in 25 of 207 patients in the captopril group and 43 of 202 patients in the placebo group (P = 0.007). Captopril showed a 48% reduction in risk of this outcome compared to placebo (95% CI, 16 to 69 percent). Additionally, captopril was associated with a 50% reduction in the risk of death, dialysis, and transplantation (95% CI, 18 to 70 percent). The study concluded that captopril is effective in slowing the decline of renal function in these patients, independent of its effect on blood pressure.
For patients with symptomatic PAD in whom single antiplatelet therapy is deemed optimal, why is clopidogrel preferred over aspirin?
A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE)
CAPRIE Steering Committee. The Lancet (November 1996)
Bottom Line: The CAPRIE trial was a randomized, blinded, international study that compared the efficacy and safety of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in patients with atherosclerotic vascular disease (manifested as either recent ischemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease). The study included 19,185 patients and followed them for 1 to 3 years. The primary outcome was a composite of reduction in the risk of ischemic stroke, myocardial infarction, or vascular death. The results showed that clopidogrel was more effective than aspirin, with an 8.7% relative-risk reduction in favor of clopidogrel (95% CI 0.6 - 16.5, p = 0.043). The safety profile of clopidogrel was similar to that of aspirin. Overall, long-term use of clopidogrel was found to be more effective in reducing the risk of clinical thrombotic events in patients with atherosclerotic vascular disease.
What’s the rationale for prescribing bisphosphonates to treat bony metastases?
Zoledronic Acid Significantly Reduces Skeletal Complications Compared With Placebo in Japanese Women With Bone Metastases From Breast Cancer: A Randomized, Placebo-Controlled Trial
Kohno N et al. Journal of Clinical Oncology (May 2005)
Bottom Line: This randomized controlled trial evaluated the efficacy and safety of zoledronic acid for the treatment of bone metastases from breast cancer. A total of 228 women were randomly assigned to receive either 4 mg zoledronic acid or placebo via 15-minute infusions every 4 weeks for 1 year. The primary outcome, skeletal-related event (SRE) rate ratio at 1 year, was defined as pathologic fracture, spinal cord compression, and radiation or surgery to bone. The adjusted SRE rate ratio, based on whether patients had or had not experienced a pathologic fracture before study entry, was 0.61 (P = .027), indicating that zoledronic acid reduced the rate of SREs by 39%. Secondary outcomes, including percentage of patients with at least one SRE, time-to-first SRE, and Andersen-Gill multiple-event analysis, also showed significant improvements in the zoledronic acid group, including a 20% reduction in the percentage of patients with at least one SRE (29.8% v 49.6% for placebo; P = .003) and a delay in time-to-first SRE. Zoledronic acid was well tolerated with no grade 3 or 4 serum creatinine increase, as measured by the National Cancer Institute Common Toxicity Criteria. In conclusion, zoledronic acid was found to be effective and safe in reducing skeletal complications in Japanese women with bone metastases from breast cancer.
Trial Files Issue #2024-15
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