Personalized Medicine: Statin Therapy for Asymptomatic Individuals

Project Title: Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study

I-HDS Member(s): Bart S. Ferket

Project Abstract:

Background: Physicians need to inform asymptomatic individuals about personalized outcomes of statin therapy for primary prevention of cardiovascular disease (CVD). However, current prediction models focus on short-term outcomes and ignore the competing risk of death due to other causes. We aimed to predict the potential lifetime benefits with statin therapy, taking into account competing risks.

Methods and Findings: A microsimulation model based on 5-y follow-up data from the Rotterdam Study, a population-based cohort of individuals aged 55 y and older living in the Ommoord district of Rotterdam, the Netherlands, was used to estimate lifetime outcomes with and without statin therapy. The model was validated in-sample using 10-y follow-up data. We used baseline variables and model output to construct (1) a web-based calculator for gains in total and CVD-free life expectancy and (2) color charts for comparing these gains to the Systematic Coronary Risk Evaluation (SCORE) charts. In 2,428 participants (mean age 67.7 y, 35.5% men), statin therapy increased total life expectancy by 0.3 y (SD 0.2) and CVD-free life expectancy by 0.7 y (SD 0.4). Age, sex, smoking, blood pressure, hypertension, lipids, diabetes, glucose, body mass index, waist-to-hip ratio, and creatinine were included in the calculator. Gains in total and CVD-free life expectancy increased with blood pressure, unfavorable lipid levels, and body mass index after multivariable adjustment. Gains decreased considerably with advancing age, while SCORE 10-y CVD mortality risk increased with age. Twenty-five percent of participants with a low SCORE risk achieved equal or larger gains in CVD-free life expectancy than the median gain in participants with a high SCORE risk.

Conclusions: We developed tools to predict personalized increases in total and CVD-free life expectancy with statin therapy. The predicted gains we found are small. If the underlying model is validated in an independent cohort, the tools may be useful in discussing with patients their individual outcomes with statin therapy.

Reference
Ferket BS, van Kempen BJ, Heeringa J, Spronk S, Fleischmann KE, Nijhuis RL, Hofman A, Steyerberg EW, Hunink MG.  Personalized prediction of lifetime benefits with statin therapy for asymptomatic individuals: a modeling study. PLoS Med. 2012;9(12):e1001361. Pubmed link

In the News
See the web-based calculator for personalized prediction of lifetime benefits with statin therapy

Anesthesia in Lung Cancer Surgery: Neuraxial Anesthesia and Patient Safety

Project Title: Patient safety and comparative effectiveness of anesthetic technique in lung resections

I-HDS Member(s): Umut Ozbek, Jashvant Poeran, and Madhu Mazumdar

Project Abstract

Background: While showing benefits over general anesthesia in other settings, the impact of neuraxial anesthetic techniques on perioperative outcomes in lung cancer patients undergoing lung surgery remains largely unstudied. We therefore studied the effect of combined neuraxial/general anesthesia (versus general anesthesia) on perioperative outcome in a large national sample of lung resection patients.

Methods: We extracted data from the national Premier Perspective claims-based database on lung resection patients (2006-2013). The main effect of interest was anesthesia type: general and combined neuraxial/general anesthesia. Patient and health care variables, as well outcome variables (complications and resource use) were compared between groups. Multivariable analyses assessed the independent impact of choice of anesthetic technique on outcomes.

Results: For 16,932 patients anesthesia type was known: 78% (n=13,190) general anesthesia and 22% (n=3,742) neuraxial/general anesthesia. Comparing general versus neuraxial/general anesthesia, incidences for the latter were lower for acute myocardial infarction (1.03% versus 0.67%, P=0.044), pulmonary complications (19.68% versus 17.93%, P=0.017), blood transfusion (13.29% versus 8.90%, P<0.0001), and mechanical ventilation (11.06% versus 8.55%, P<0.0001). Neuraxial/general (versus general) anesthesia had lower adjusted odds of blood transfusion (OR=0.74, CI 0.61-0.89), while higher odds were seen for deep vein thrombosis (OR 1.59, CI 1.05-2.43), and pulmonary embolism (OR 1.66, CI 1.07-2.6.)

Conclusions: This study shows the consequences on perioperative complications of adding neuraxial anesthesia to general anesthesia in lung resections among cancer patients such as decreasing blood product transfusion requirement but increasing thromboembolic risks. Additional studies are needed to elucidate mechanisms by which neuraxial anesthesia may affect these outcomes.

Tranexamic Acid in Orthopedic Surgery: Reducing Blood Transfusions While Not Increasing Complications

Project Title: Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety

I-HDS Member(s): Jashvant Poeran, Rehana Rasul, and Madhu Mazumdar

Project Abstract

Objective: To determine the effectiveness and safety of perioperative tranexamic acid use in patients undergoing total hip or knee arthroplasty in the United States.

Design: Retrospective cohort study; multilevel multivariable logistic regression models measured the association between tranexamic acid use in the perioperative period and outcomes.

Setting: 510 US hospitals from the claims based Premier Perspective database for 2006-12.

Participants: 872,416 patients who had total hip or knee arthroplasty.

Intervention: Perioperative intravenous tranexamic acid use by dose categories (none, ≤ 1000 mg, 2000 mg, and ≥ 3000 mg).

Main Outcome Measures: Allogeneic or autologous transfusion, thromboembolic complications (pulmonary embolism, deep venous thrombosis), acute renal failure, and combined complications (thromboembolic complications, acute renal failure, cerebrovascular events, myocardial infarction, in-hospital mortality).

Results: While comparable regarding average age and comorbidity index, patients receiving tranexamic acid (versus those who did not) showed lower rates of allogeneic or autologous transfusion (7.7% v 20.1%), thromboembolic complications (0.6% v 0.8%), acute renal failure (1.2% v 1.6%), and combined complications (1.9% v 2.6%); all P<0.01. In the multilevel models, tranexamic acid dose categories (versus no tranexamic acid use) were associated with significantly (P<0.001) decreased odds for allogeneic or autologous blood transfusions (odds ratio 0.31 to 0.38 by dose category) and no significantly increased risk for complications: thromboembolic complications (odds ratio 0.85 to 1.02), acute renal failure (0.70 to 1.11), and combined complications (0.75 to 0.98).

Conclusions: Tranexamic acid was effective in reducing the need for blood transfusions while not increasing the risk of complications, including thromboembolic events and renal failure. Thus our data provide incremental evidence of the potential effectiveness and safety of tranexamic acid in patients requiring orthopedic surgery

Reference
Poeran J, Rasul R, Suzuki S, Danninger T, Mazumdar M, Opperer M, Boettner F, Memtsoudis SG. Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety. BMJ. 2014;349:g4829. Pubmed link

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MDLinx ”Tranexamic acid use and postoperative outcomes in patients undergoing total hip or knee arthroplasty in the United States: retrospective analysis of effectiveness and safety”