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  • Measure Summary
  • NQMC:006321
  • Jan 2011

Percent time in therapeutic INR range (TTR): mean TTR achieved among patients who received prescriptions for warfarin and had sufficient INR values to calculate TTR.

Rose A. Staff physician, Bedford VA Medical Center. Investigator, VA Center for Health Quality, Outcomes, and Economic Research at the Bedford VA. Assistant Professor, Boston University School of Medicine. Percent time in therapeutic INR range (TTR). 2010 Oct 7. 8 p.

This is the current release of the measure.

The measure developer reaffirmed the currency of this measure in March 2016.

Primary Measure Domain

Clinical Quality Measures: Outcome

Secondary Measure Domain

Does not apply to this measure

Description

This measure is used to assess the mean therapeutic international normalized ratio (INR) range (TTR) achieved among patients who received prescriptions for warfarin and had sufficient INR values to calculate TTR.

Rationale

Millions of patients in the United States use warfarin to prevent strokes or to prevent or treat venous thromboembolism. Warfarin is highly effective, and has been in clinical use for over 50 years. However, warfarin is difficult to manage because it has many possible interactions with diet, other drugs, and comorbid conditions that may destabilize anticoagulation control. The possible consequences of insufficient or excessive anticoagulation are extremely serious and often fatal, making it imperative to pursue good control.

The international normalized ratio (INR) test is the laboratory test used to determine the degree to which the patient's coagulation has been successfully suppressed by the vitamin K antagonist (VKA). For most patients, the goal is to keep the INR between 2 and 3, which roughly corresponds to the blood taking 2 to 3 times as long to clot as would a normal person's blood. This level of anticoagulation has been shown to maximize benefit (i.e., protect patients from blood clots) while minimizing risk (i.e., risk of hemorrhage attributable to excessive anticoagulation). Therapeutic INR range (TTR) is a way of summarizing INR control over time.

TTR has been followed before, mostly in the setting of clinical trials where it is used to evaluate the effectiveness of warfarin therapy, particularly when warfarin is being compared to some other strategy. However, TTR has not previously been used as a quality measure – in fact, there has been a general lack of quality measurement in oral anticoagulation. There is much evidence that better anticoagulation control (i.e., higher TTR) can protect patients from severe or even fatal adverse events.

Evidence for Rationale

Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of the vitamin K antagonists: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):160S-98S. [419 references] PubMed External Web Site Policy

Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, Healey JS, Yusuf S, ACTIVE W Investigators. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008 Nov 11;118(20):2029-37. [21 references] PubMed External Web Site Policy

Rose A. Staff physician, Bedford VA Medical Center. Investigator, VA Center for Health Quality, Outcomes, and Economic Research at the Bedford VA. Assistant Professor, Boston University School of Medicine. Percent time in therapeutic INR range (TTR). 2010 Oct 7. 8 p.

Rose AJ, Berlowitz DR, Frayne SM, Hylek EM. Measuring quality of oral anticoagulation care: extending quality measurement to a new field. Jt Comm J Qual Patient Saf. 2009 Mar;35(3):146-55. [115 references] PubMed External Web Site Policy

Rosendaal FR, Cannegieter SC, van der Meer FJ, Briet E. A method to determine the optimal intensity of oral anticoagulant therapy. Thromb Haemost. 1993 Mar 1;69(3):236-9. PubMed External Web Site Policy

van Leeuwen Y, Rosendaal FR, Cannegieter SC. Prediction of hemorrhagic and thrombotic events in patients with mechanical heart valve prostheses treated with oral anticoagulants. J Thromb Haemost. 2008 Mar;6(3):451-6. PubMed External Web Site Policy

van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006 May;129(5):1155-66. [97 references] PubMed External Web Site Policy

Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol. 2005 Feb;128(4):513-9. PubMed External Web Site Policy

White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, Albers GW. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007 Feb 12;167(3):239-45. PubMed External Web Site Policy

Primary Health Components

Oral anticoagulation; warfarin; international normalized ratio (INR); therapeutic INR range (TTR)

Denominator Description

All patients, 18 years and older, who received prescriptions for warfarin and had sufficient international normalized ratio (INR) values to calculate therapeutic INR range (TTR) (see the related "Denominator Inclusions/Exclusions" field)

Numerator Description

Mean therapeutic international normalized ratio (INR) range (TTR) achieved among patients who received prescriptions for warfarin and had sufficient INR values to calculate TTR

Type of Evidence Supporting the Criterion of Quality for the Measure

  • A clinical practice guideline or other peer-reviewed synthesis of the clinical research evidence
  • One or more research studies published in a National Library of Medicine (NLM) indexed, peer-reviewed journal

Additional Information Supporting Need for the Measure

  • The number of dispensed outpatient prescriptions for warfarin in the United States (U.S.) increased from 21 million in 1998 to nearly 31 million in 2004. While there are no firm estimates for the number of patients receiving warfarin, even assuming 12 prescriptions per year for all patients, this would suggest approximately 2.5 million users in 2004, or approximately 1% of the U.S. population. In fact, patients may not receive 12 prescriptions per year (because of 90-day prescriptions and the like), so this number may be closer to 2% of the U.S. population. Also, these estimates do not account for the fact that the number of prescriptions for warfarin probably has continued to increase since 2004.
  • Poor anticoagulation control greatly increases the risk of stroke, venous thromboembolism (VTE), major hemorrhage, and death.
  • Events such as stroke, major hemorrhage, and VTE are extremely expensive to treat. In fact, stroke frequently leads to lifelong institutionalization, which is extremely expensive.
  • Veterans Administration (VA) data have shown wide variation in therapeutic international normalized ratio (INR) range (TTR) among sites of care. In addition, the mean TTR achieved in the VA system (58%) leaves much room for improvement. Most studies suggest that the overall quality of anticoagulation control is also poor outside the VA. The combination of poor overall quality of care and variability in performance strongly argues for the need to measure quality on an ongoing basis.

Evidence for Additional Information Supporting Need for the Measure

Connolly SJ, Pogue J, Eikelboom J, Flaker G, Commerford P, Franzosi MG, Healey JS, Yusuf S, ACTIVE W Investigators. Benefit of oral anticoagulant over antiplatelet therapy in atrial fibrillation depends on the quality of international normalized ratio control achieved by centers and countries as measured by time in therapeutic range. Circulation. 2008 Nov 11;118(20):2029-37. [21 references] PubMed External Web Site Policy

O'Brien CL, Gage BF. Costs and effectiveness of ximelagatran for stroke prophylaxis in chronic atrial fibrillation. JAMA. 2005 Feb 9;293(6):699-706. PubMed External Web Site Policy

Rose A. Staff physician, Bedford VA Medical Center. Investigator, VA Center for Health Quality, Outcomes, and Economic Research at the Bedford VA. Assistant Professor, Boston University School of Medicine. Percent time in therapeutic INR range (TTR). 2010 Oct 7. 8 p.

Rose AJ, Berlowitz DR, Frayne SM, Hylek EM. Measuring quality of oral anticoagulation care: extending quality measurement to a new field. Jt Comm J Qual Patient Saf. 2009 Mar;35(3):146-55. [115 references] PubMed External Web Site Policy

Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs Study To Improve Anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes. 2011 Jan 1;4(1):22-29. PubMed External Web Site Policy

van Leeuwen Y, Rosendaal FR, Cannegieter SC. Prediction of hemorrhagic and thrombotic events in patients with mechanical heart valve prostheses treated with oral anticoagulants. J Thromb Haemost. 2008 Mar;6(3):451-6. PubMed External Web Site Policy

van Walraven C, Jennings A, Oake N, Fergusson D, Forster AJ. Effect of study setting on anticoagulation control: a systematic review and metaregression. Chest. 2006 May;129(5):1155-66. [97 references] PubMed External Web Site Policy

Veeger NJ, Piersma-Wichers M, Tijssen JG, Hillege HL, van der Meer J. Individual time within target range in patients treated with vitamin K antagonists: main determinant of quality of anticoagulation and predictor of clinical outcome. A retrospective study of 2300 consecutive patients with venous thromboembolism. Br J Haematol. 2005 Feb;128(4):513-9. PubMed External Web Site Policy

White HD, Gruber M, Feyzi J, Kaatz S, Tse HF, Husted S, Albers GW. Comparison of outcomes among patients randomized to warfarin therapy according to anticoagulant control: results from SPORTIF III and V. Arch Intern Med. 2007 Feb 12;167(3):239-45. PubMed External Web Site Policy

Wysowski DK, Nourjah P, Swartz L. Bleeding complications with warfarin use: a prevalent adverse effect resulting in regulatory action. Arch Intern Med. 2007 Jul 9;167(13):1414-9. [35 references] PubMed External Web Site Policy

Extent of Measure Testing

A study of 124,551 patients who received outpatient oral anticoagulation from 100 Veterans Administration (VA) sites of care for indications other than valvular heart disease demonstrated that risk-adjusted therapeutic international normalized ratio (INR) range (TTR) can be used as a quality indicator for oral anticoagulation care. Risk-adjusted TTR is feasible to measure and is relatively consistent from year to year, suggesting that it is measuring an aspect of quality of care that is stable over time. This measure could be used by the VA or other integrated systems of care to profile annual performance and serve as an aid and impetus for quality improvement.

Evidence for Extent of Measure Testing

Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs Study To Improve Anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes. 2011 Jan 1;4(1):22-29. PubMed External Web Site Policy

State of Use

Current routine use

Current Use

Internal quality improvement

Quality of care research

Measurement Setting

Ambulatory/Office-based Care

Community Health Care

Home Care

Managed Care Plans

Rehabilitation Centers

Residential Care Facilities

Rural Health Care

Skilled Nursing Facilities/Nursing Homes

Professionals Involved in Delivery of Health Services

Advanced Practice Nurses

Nurses

Pharmacists

Physician Assistants

Physicians

Least Aggregated Level of Services Delivery Addressed

Clinical Practice or Public Health Sites

Statement of Acceptable Minimum Sample Size

Unspecified

Target Population Age

Age greater than or equal to 18 years

Target Population Gender

Either male or female

National Quality Strategy Aim

Better Care

National Quality Strategy Priority

Prevention and Treatment of Leading Causes of Mortality

IOM Care Need

Getting Better

Living with Illness

IOM Domain

Effectiveness

Case Finding Period

Unspecified

Denominator Sampling Frame

Patients associated with provider

Denominator (Index) Event or Characteristic

Diagnostic Evaluation

Patient/Individual (Consumer) Characteristic

Therapeutic Intervention

Denominator Time Window

Time window brackets index event

Denominator Inclusions/Exclusions

Inclusions
Patients, 18 years and older, who received prescriptions for warfarin and had sufficient international normalized ratio (INR) values to calculate therapeutic INR range (TTR)

Include only patients who had at least two valid intervals for calculating percent time in TTR. A valid interval consists of two INR values separated by 56 days or less, without an intervening hospitalization.

Note: All patients should be held to the standard target range of 2 to 3. If specific information is available about target ranges, it is recommended to include patients with a target range of 2.5 to 3.5, but to calculate their TTR separately.

Exclusions

  • Patients who only recorded INR values 1.2 and lower
  • Patients whose primary indication to receive warfarin was valvular heart disease

Note: Refer to the articles in the "Companion Documents" field for additional details regarding the denominator inclusions/exclusions.

Exclusions/Exceptions

Unspecified

Numerator Inclusions/Exclusions

Inclusions
Mean therapeutic international normalized ratio (INR) range (TTR) achieved among patients who received prescriptions for warfarin and had sufficient INR values to calculate TTR

Exclusions
Unspecified

Numerator Search Strategy

Fixed time period or point in time

Data Source

Laboratory data

Pharmacy data

Type of Health State

Physiologic Health State (Intermediate Outcome)

Instruments Used and/or Associated with the Measure

Unspecified

Measure Specifies Disaggregation

Does not apply to this measure

Scoring

Mean/Median

Interpretation of Score

Desired value is a higher score

Allowance for Patient or Population Factors

Risk adjustment devised specifically for this measure/condition

Description of Allowance for Patient or Population Factors

The risk-adjustment model derived for this measure allows for the following variables:

  • Female sex
  • Age group (years): 20-54; 55-59; 60-64; 65-69; 70-74; 75+
  • Race/ethnicity: Non-hispanic White; Non-hispanic Black; Hispanic; Asian; Native American; Other/Unknown
  • Percentage poverty in zip code of residence (quintile): Wealthiest (0-5.9); Wealthy (5.9-9.0); Moderate (9.0-12.6); Poor (12.6-17.8); Poorest (17.8-100)
  • Driving distance from nearest Veterans Administration (VA) facility in miles (quintile): Nearest (0-3.1); Near (3.1-6.0); Moderate (6.0-10.5); Far (10.5-20.3); Furthest (greater than 20.3)
  • Primary indication for warfarin: Atrial fibrillation; Venous thromboembolism; All others combined
  • Physical comorbid conditions: Cancer (newly diagnosed); Chronic kidney disease; Chronic liver disease; Chronic lung disease; Coronary artery disease; Diabetes; Epilepsy; Heart failure; Hyperlipidemia; Hypertension; Pain disorders; Peripheral arterial disease
  • Mental comorbid conditions: Alcohol abuse; Anxiety; Bipolar disorder; Dementia; Major depression; Post-traumatic stress disorder; Schizophrenia; Substance abuse (non-alcohol)
  • Number of non-warfarin medications: 0-7; 8-11; 12-15; 16+
  • Number of hospitalizations during inception period: None; 1; 2+

Refer to the articles in the "Companion Documents" field for more details on the risk-adjustment model.

Standard of Comparison

External comparison at a point in, or interval of, time

External comparison of time trends

Internal time comparison

Original Title

Percent time in therapeutic INR range (TTR).

Submitter

Rose, Adam, MD, MSc, FACP - Independent Author(s)

Developer

Rose, Adam, MD, MSc, FACP; Berlowitz, Dan, MD, MPH; Reisman, Joel, AB; Ash, Arlene, PhD; Ozonoff, Al, PhD; Hylek, Elaine, MD, MPH - Independent Author(s)

U.S. Department of Veterans Affairs, Health Services Research and Development Service, Center for Health Quality, Outcomes and Economic Research (CHQOER) - Government Affiliated Research Institute

Funding Source(s)

U.S. Department of Veterans Affairs, Health Services Research and Development Service -- Career Development Award (to Dr. Rose)

Composition of the Group that Developed the Measure

Adam Rose, MD, MSc, FACP; Elaine Hylek, MD, MPH (Boston University School of Medicine, Section of General Internal Medicine); Al Ozonoff, PhD (Boston Children's Hospital, Biostatistics); Arlene Ash, PhD (University of Massachusetts School of Medicine); Joel Reisman (Statistical Programmer, Bedford VA Medical Center); Dan Berlowitz, MD, MPH (Bedford VA Medical Center, Boston University School of Medicine, Boston University School of Public Health, Department of Health Policy and Management)

Financial Disclosures/Other Potential Conflicts of Interest

Dr. Hylek has received honoraria from Bayer and Bristol-Myers Squibb, and has served on advisory boards for Boehringer-Ingelheim, Bristol-Myers Squibb, Merck, and sanofi-aventis. None of the other developers of this measure report any potential conflicts of interest.

Adaptation

This measure was not adapted from another source.

Date of Most Current Version in NQMC

2011 Jan

Measure Maintenance

Unspecified

Date of Next Anticipated Revision

Unspecified

Measure Status

This is the current release of the measure.

The measure developer reaffirmed the currency of this measure in March 2016.

Source(s)

Rose A. Staff physician, Bedford VA Medical Center. Investigator, VA Center for Health Quality, Outcomes, and Economic Research at the Bedford VA. Assistant Professor, Boston University School of Medicine. Percent time in therapeutic INR range (TTR). 2010 Oct 7. 8 p.

Measure Availability

Source not available electronically.

For more information, contact Dr. Adam Rose at adamrose@bu.edu.

Companion Documents

The following are available:

  • Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Risk-adjusted percent time in therapeutic range as a quality indicator for outpatient oral anticoagulation: results of the Veterans Affairs Study To Improve Anticoagulation (VARIA). Circ Cardiovasc Qual Outcomes 2011 Jan 1;4(1):22-29. This document is available from the American Heart Association Web site External Web Site Policy.
  • Rose AJ, Hylek EM, Ozonoff A, Ash AS, Reisman JI, Berlowitz DR. Patient characteristics associated with oral anticoagulation control: results of the Veterans Affairs Study to Improve Anticoagulation (VARIA). J Thromb Haemost 2010 Oct;8(10):2182-91.

For more information, please contact Dr. Adam Rose at adamrose@bu.edu.

NQMC Status

This NQMC summary was completed by ECRI Institute on April 14, 2011. The information was verified by the measure developer on April 21, 2011.

This NQMC summary was retrofitted into the new template on May 20, 2011.

The information was reaffirmed by the measure developer on March 17, 2016.

Copyright Statement

This measure represents the work of the authors alone and does not necessarily represent the official views or polices of the Department of Veterans Affairs. For further information regarding this measure, contact Adam Rose at adam.rose@va.gov.

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