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In this section, we will highlight the key high-impact studies, updates, and analyses published in medicine during the past week.
A Pharmacogenetic versus a Clinical Algorithm for Warfarin Dosing
A Randomized Trial of Genotype-Guided Dosing of Warfarin
Warfarin metabolism has been previously shown to be partially genetically determined with polymorphisms CYP2C9*2, CYP2C9*3, and VKORC1 (−1639G→A) conferring different pharmcokinetic rates of metabolism. This past week in NEJM, two multicenter, randomized trials compared genotype guided algorithms of warfarin induction compared to a clinical algorithm or a standard loading dose. In the first trial, 1015 patients were randomized to warfarin induction algorithms using either clinical features alone or clinical features with genotyping and compared time in therapeutic range during the first four weeks of therapy. This trial found no difference in mean time in therapeutic range (45.2% for genotype-guided group vs. 45.4% for clinically-guided group, p = 0.91) and there was no significant difference in major bleeding, thromboembolism, or other complications. The second trial randomized 455 patients to a genotype-guided algorithm vs. a set 3-day loading dose and compared time in therapeutic range during the first twelve weeks of therapy. This study found a difference in mean time in therapeutic range (67.4% for genotype-guided group vs. 60.3% for clinically-guided group, p<0.001) with fewer instances of supratherapeutic INR > 4 in the genotype-guided group. Differences in the study include different follow-up times, control groups, genotyping assays, and patient demographics. Genotyping to guide warfarin induction remains controversial.
Effect of CPAP on Blood Pressure in Patients With Obstructive Sleep Apnea and Resistant Hypertension
Significant subsets of patients with resistant hypertension have obstructive sleep apnea (OSA). In this multiple center, randomized, open-label trial, 194 patients with resistant hypertension and OSA were randomized to CPAP with standard blood pressure control medications vs. blood pressure control medications alone and blood pressure was tracked for 12 weeks. The CPAP group achieved a greater decrease in 24-hour mean blood pressure (3.1 mm Hg [95% CI, 0.6 to 5.6]; P = .02) and 24-hour DBP (3.2 mm Hg [95% CI, 1.0 to 5.4]; P = .005), but not in 24-hour SBP (3.1 mm Hg [95% CI, −0.6 to 6.7]; P = .10) compared with the control group. More frequent and longer duration of CPAP use was associated with greater change in 24-hour mean blood pressure (r = 0.29, P = .006), SBP (r = 0.25; P = .02), and DBP (r = 0.30, P = .005). There was a small but significant decrease in blood pressure with the initiation of CPAP in patients with OSA and resistant hypertension.
Bariatric surgery has been characterized to decrease insulin dependence and cause significant weight loss immediately after surgery however limited long term studies have been performed. In this retrospective analysis of a multicenter observational cohort, investigators identified 2458 patients undergoing first time Roux-en-Y gastric bypass (RYGB) or laparoscopic adjustable gastric banding (LAGB). At three years, median weight loss was 41kg (31.5%), with 216 (67.5%) RYGB patients and 28 (28.6%) LAGB patients experiencing partial remission of diabetes. Improvements in dyslipidemia and hypertension were also seen. The majority of weight was lost during the first year after procedure.
Cangrelor is a potent, rapid-acting, reversible intravenous platelet inhibitor used during percutaneous intervention for acute coronary syndrome. In this retrospective analysis of three randomized, control trials comparing cangrelor vs. clopidogrel vs. placebo, investigators assessed cangrelor’s efficacy and prespecified primary efficacy composite of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis at 48 h in 24,910 patients. Cangrelor reduced the odds of the primary outcome by 19% (3·8% for cangrelor vs 4·7% for control; odds ratio [OR] 0·81, 95% CI 0·71—0·91, p=0·0007), and stent thrombosis by 41% (0·5% vs 0·8%, OR 0·59, 95% CI 0·43—0·80, p=0·0008). There was no difference in the primary safety outcome (0·2% in both groups), in GUSTO moderate bleeding (0·6% vs 0·4%), or in transfusion (0·7% vs 0·6%), but cangrelor increased GUSTO mild bleeding (16·8% vs 13·0%, p<0·0001). Cangrelor seems to decrease the risk of thrombotic events but have an increased risk for bleeding events compared to clopidogrel.
By David Ouyang
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