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Statin does not protect against acute kidney injury following cardiac surgery
Although statins affect mechanisms that lead to postoperative acute kidney injury (AKI), observational studies have failed to demonstrate a consistent effect of statin therapy on the risk of AKI after cardiac surgery. The Statin AKI Cardiac Surgery randomized control trial sought to determine if high-dose, short-term atorvastatin reduced the risk of AKI following cardiac surgery. This double-blind, placebo-controlled, single center trial, evaluated high-dose perioperative atorvastatin on AKI in 615 patients undergoing elective coronary artery bypass surgery, valvular heart surgery, or ascending aortic surgery. The intervention arm received atorvastation 80 mg the day prior to surgery, 40mg day of surgery, and 40 mg daily for the duration of hospitalization. Patients were randomized with stratification for prior statin use, presence of chronic kidney disease (GFR<60 ml/min/1.73 m2), and history or diabetes. The primary outcome of AKI was defined as an increase of 0.3 mg/dL in serum creatinine or initiation of renal replacement therapy within 48 hours of surgery. The study was terminated after a second interim analysis for concern of increased risk of AKI among statin naïve patients and for futility among patients who were previously on a statin.
High-dose statin therapy does not reduce the risk of AKI following cardiac surgery.
Summarized by Lauren E. Thompson and Steven M. Bradley
▸ Billings FT, Hendricks PA, Schildcrout JS, et al. High-Dose Perioperative Atorvastatin and Acute Kidney Injury Following Cardiac Surgery: A Randomized Clinical Trial. JAMA 2016;315:877–88.
Mailing Nicotine Patches Improves Smoking Abstinence
Although clinical trials of nicotine replacement therapy (NRT) have consistently demonstrated higher rates of smoking cessation, the effectiveness of NRT may be lower in real-world settings, especially in the absence of behavioral support. Accordingly, there is a need for randomized clinical trials to evaluate the effectiveness of NRT alone. Cunningham et al conducted a randomized trial on adult smokers across Canada testing the impact of mailing nicotine patches to smokers without behavioral support on quit rates. A total of 500 adults smoking more than 10 cigarettes daily were randomized to the experimental arm (mailed a 5-week supply of nicotine patches) or control arm (no nicotine patches mailed). The primary outcome was self-reported abstinence from smoking at 6 months. Self-reported nicotine abstinence rates were higher in the experimental arm (OR 2.65, 95% CI 1.44–4.89, p=0.002). Of those who claimed abstinence, biochemical validation via saliva analysis for cotinine was available in 50.9%. Biochemically validated abstinence at 6 months was found in 14 patients (2.8%) of 500 in the experimental cohort compared to 5 (1.0%) of 499 in the control group (OR 2.85, 95% CI 1.02–7.96, p=0.046).
This work suggests access to nicotine patches alone, without concurrent behavioral support, promotes tobacco cessation. However, low rates of biochemically validated smoking cessation limits the significance of the study findings.
Summarized by Amneet Sandhu and Steven M. Bradley
▸ Cunningham JA, Kushnir V, Selby P, et al. Effect of Mailing Nicotine Patches on Tobacco Cessation Among Adult Smokers: A Randomized Clinical Trial. JAMA Intern Med 2016;176:184–90.
Early Disclosure of Trial Results Limits Insights on Weight Loss Drug
Obesity is increasingly common and contributes significantly to poor health. Drug therapies for obesity have demonstrated efficacy in weight loss, but have yet to show improvement in cardiovascular outcomes, and at times have caused cardiovascular harm that required drug removal from the market. As a result, prior to approval of the new weight loss medication naltrexone-buproprion, the Federal Drug Administration (FDA) required a placebo controlled trial evaluating cardiovascular outcomes (Major adverse cardiovascular events (MACE) of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina, and all-cause mortality). To minimize delays to drug approval, a 2-step safety evaluation was proposed in which confidential interim trial results would be used to secure FDA approval while final trial results would be released at study completion. The resulting multicenter, placebo-controlled trial randomized 8 910 overweight or obese patients at increased risk of cardiovascular events in a 1:1 fashion to naltrexone-buproprion or placebo. Due to public disclosure of interim study by the study sponsor, termination of the trial was recommended for breach of confidentiality. Prior to termination, 50% of planned events (time to first MACE) had occurred which demonstrated 102 (2.3%) events in placebo and 90 (2.0%) events in naltrexone-bupropion groups (HR 0.88; adjusted 99.7% CI 0.57–1.34). In a post-hoc analysis evaluating changes in blood pressure and heart rate at 16 weeks, when adherence to the treatment regimen was high, there was an increase in mean blood pressure by 0.46 mmHg (95% CI 0.01–0.92 mm Hg) and an increase in heart rate by 0.45/min (95% CI 0.11/min to 0.78/min) in naltrexone-bupropion compared to placebo.
This is the first large clinical trial to be terminated early due to a breach of confidentiality resulting from public release of interim data. The primary non-inferiority endpoint was achieved, but given the early termination, prespecified cardiovascular safety endpoints were unable to be assessed. As a result, another large and expensive trial to evaluate the cardiovascular safety of this weight loss medication is currently underway.
Summarized by Lauren E. Thompson and Steven M. Bradley
▸ Nissen SE, Wolski KE, Prcela L, et al. Effect of Naltrexone-Bupropion on Major Adverse Cardiovascular Events in Overweight and Obese Patients With Cardiovascular Risk Factors: A Randomized Clinical Trial. JAMA 2016;315:990–1004.
Competing interests None.
Provenance and peer review Commissioned; internally peer reviewed.