- Email: [email protected]
Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial
Relationship between Risk Factor Control and Compliance with a Lifestyle Modification Program in the Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis Trial Tanya N. Turan, MD, MS,* Sami Al Kasab, MD,* Azhar Nizam, MS,† Michael J. Lynn, MS,† Jamie Harrell, BS,* Colin P. Derdeyn, MD,‡ David Fiorella, MD, Phd,§ L. Scott Janis, PhD,‖ Bethany F. Lane, MSN,† Jean Montgomery, RN,† and Marc I. Chimowitz, MBChB* for the SAMMPRIS Investigators
Background: Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. Methods: SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Results: Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non–high-density lipoprotein, nonsmoking, and
From the *Department of Neurology, Medical University of South Carolina, Charleston, South Carolina; †Department of Public Health, Emory University, Atlanta, Georgia; ‡Department of Radiology, University of Iowa, Iowa City, Iowa; §Department of Neurosurgery, State University of New York at Stony Brook, Stony Brook, New York; and ‖Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland. Received July 26, 2017; accepted October 13, 2017. Grant support: This study was funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke. In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health U01 NS058728, provided local support for the evaluation of patients in the trial: Medical University of South Carolina (UL1RR029882), University of Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and University of California, San Francisco (UL1RR024131). Address correspondence to Sami Al Kasab, MD, Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas St, Charleston, SC 29425. E-mail: [email protected]. 1052-3057/$ - see front matter Published by Elsevier Inc. on behalf of National Stroke Association. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.10.017
Journal of Stroke and Cerebrovascular Diseases, Vol. 27, No. 3 (March), 2018: pp 801–805
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T.N. TURAN ET AL.
802 exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. Conclusion: SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors. Key Words: Stroke—intracranial atherosclerosis—medical management—compliance—lifestyle modification program. Published by Elsevier Inc. on behalf of National Stroke Association.
Introduction The Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial was the first stroke prevention trial to employ protocol-driven multimodal aggressive management of multiple vascular risk factors, including elevated blood pressure, cholesterol, diabetes mellitus (DM), smoking, weight, and exercise. The results of the trial showed that aggressive medical management was superior to stenting for stroke prevention in patients with recently symptomatic severe intracranial stenosis,1-3 and that good risk factor control was associated with better outcomes.4 The SAMMPRIS Trial was also the first vascular disease prevention trial to incorporate a commercially available telephonic lifestyle modification program for study participants to enhance risk factor control. Although lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack,5-7 to our knowledge, such programs have not been evaluated in the setting of a vascular prevention clinical trial. In the present study, we sought to determine if utilization of a lifestyle modification program improved risk factor control in the setting of a clinical trial.
Methods The overall design of SAMMPRIS and its aggressive medical management protocols have been described previously.1,8 Funded by the National Institutes of Health, SAMMPRIS was an investigator-initiated and designed phase III randomized multicenter trial in which 451 patients were randomized at 50 sites in the United States. Institutional review boards at all 50 participating sites approved the study protocol. Aggressive medical therapy alone versus percutaneous transluminal angioplasty and stenting with the wingspan stent system plus aggressive medical therapy versus stenting plus aggressive medical therapy. Aggressive risk factor management primarily targeted systolic blood pressure (SBP) less than 140 mm Hg and low-density lipoprotein (LDL) less than 70 mg/dL. Secondary risk factors targeted included diabetes mellitus, physical inactivity, weight, and smoking. Using a commercially available lifestyle mod-
ification program (INTERVENT), all subjects received coaching on healthy lifestyle behaviors at regularly schedule times throughout the study at no charge. Lifestyle coaches provided individualized risk factor counseling (by telephone or Internet) twice a month for 6 months and monthly thereafter. For this analysis, subjects with fewer than 3 expected lifestyle-coaching calls (e.g., those who left the study early due to end point, or withdrew consent) were excluded. There was no prespecified definition of compliance. Therefore, subjects were considered “compliant” if they completed more than the mean percentage of expected calls or more. Subjects were considered “noncompliant” if they completed less than the mean percentage of expected calls or refused to participate in INTERVENT at all. Risk factor values for each subject during follow-up were recorded at baseline, 30 days, 4 months, and every 4 months thereafter. Mean risk factor values (SBP, LDL, non–high-density lipoprotein [HDL], hemoglobin A1c [HbA1c], body mass index [BMI]) or percent in-target (physical activity and smoking cessation) were compared between compliant and noncompliant subjects, using t tests and chi-square tests. To account for baseline differences between groups, risk factor changes from baseline to follow-up were also compared between the groups using t tests, Fisher’s exact tests, and chi-square tests.
Results The median percentage of expected calls that were completed by the subjects was 78.5%. Therefore, “compliant” subjects (n = 201) were defined as those who completed 78.5% or more expected calls from lifestyle coaches and “noncompliant” subjects (n = 200) completed less than 78.5% of calls or refused to participate at all. Baseline characteristics are summarized in Table 1. African-Americans were found to be less compliant with INTERVENT (9% compliant vs. 15% noncompliant) when compared to whites (38% compliant vs. 32% noncompliant) (P = .04). There was no significant difference with regard to compliance among assigned treatment groups (P = .29). As shown in Figure 1, compliant subjects had better control than noncompliant subjects of LDL, non-HDL, and HgA1c at baseline (P < .05). At several time points in the study follow-up period, compliant subjects also had better risk factor control than noncompliant subjects for
SAMMPRIS RISK FACTOR CONTROL AND LIFESTYLE MODIFICATION
Table 1. Comparison of baseline characteristics in the compliant and noncompliant treatment groups
Age (years) Race White AfricanAmerican Sex Male Female Treatment assignment Medical PTAS plus medical
Compliant (n = 201)
Non-compliant (n = 200)
60.7 (±10.8)
58.7 (±11.8)
154 (38%) 37 (9%)
128 (32%) 59 (15%)
P value .08* .04†
(48%) (53%)
P = .04), and the change in SBP from baseline to 24 months (−18.4 ± 21.6 mmHg, n = 171 vs. −11.2 ± 23.5 mmHg, n = 130; P = .006). Compliant and noncompliant subjects also differed in the change from baseline to 36 months for diastolic blood pressure (−6.2 ± 11.8 mmHg, n = 113 vs. −4.2 ± 12.5 mm Hg, n = 60; P = .02) and HDL (10.3 ± 14.9 mg/ dL, n = 55 vs. 1.6 ± 10.5 mg/dL, n = 17; P = .03).
Discussion .09‡
134 (33%) 67 (17%)
803
117 (30%) 83 (21%)
.29 ‡
Abbreviation: PTA, percutaneous transluminal angioplasty and stenting. *t Test. †Fisher’s exact test. ‡Chi-square P value.
LDL, SBP, HgA1c, non-HDL, non-smoking, and exercise (P < .05), but there was no difference for BMI. There was a significant difference between compliant and noncompliant subjects in the change in HbA1c from baseline to 6 months (−.7% ± 1.9%, n = 59 vs. .2% ± 2.7%, n = 58;
These post hoc analyses of patients in the SAMMPRIS Trial show that adherence to a lifestyle modification program was associated with significantly better control of almost all vascular risk factors. To our knowledge, this is the first study to evaluate the impact of incorporating a lifestyle modification program into a large secondary prevention vascular clinical trial and show that such programs can improve intensive risk factor control when used by clinical trial participants. Our results are consistent with a previous small cohort study of patients with stroke, transient ischemic attack, and carotid artery stenosis, which reported that active participation in lifestyle health coaching is associated with improved vascular risk factor control.5 Gordon et al also found that patients with conventional coronary heart disease risk factors could achieve risk factor control within 12 weeks of initiating therapeutic lifestyle changes without medications when supported by a community-based lifestyle management program.6 Another study, by Daubenmier et al, evaluated the impact
Figure 1. Risk factor control in compliant versus noncompliant subjects. Abbreviations: BMI, body mass index; HgA1c, hemoglobin A1c; LDL, lowdensity lipoprotein; non-HDL, non–high-density lipoprotein; SBP, systolic blood pressure.
804
of a health insurance-based Multisite Cardiac Lifestyle Intervention Program on changes in coronary risk and psychosocial factors at 3 months in 869 nonsmoking patients with cardiovascular heart disease.9 Daubenmier et al found that improvements in stress management, exercise, and dietary fat intake were significantly associated with improvements in coronary risk (reduction in weight, LDL, and increased exercise) and psychosocial factors. Although our findings suggest that compliance with the lifestyle modification program led to overall better risk factor control and better outcome, we cannot rule out the confounding possibility that patients who were noncompliant with INTERVENT were noncompliant in general (e.g., with medications) and would have worse risk factor control as a result; other research has suggested that lifestyle modification alone and without medications improves risk factor control. A study by Wadden et al compared the effect of lifestyle modification and pharmacotherapy for obesity.10 The investigators randomly assigned 224 obese adults to receive medical therapy alone, lifestyle modification alone, and pharmacotherapy in addition to lifestyle modification. The study showed that subjects receiving combined therapy lost 12.1 ± 7.4 kg; those treated with lifestyle modification alone lost 6.7 ± 7.9 kg; and those with pharmacotherapy alone lost 5.0 ± 7.4 kg. Additionally, the study discussed by Gordon et al showed that lifestyle modification alone without medical therapy can lead to vascular risk factor control at 12 weeks.6 Because we did not collect data on medication compliance, we cannot exclude this possibility. However, efforts to improve compliance with risk factor control in general (e.g., providing study medications to subjects at no cost and frequent follow-up visits) would be expected to minimize some common compliance issues.
Conclusion Compliance with the lifestyle modification program in SAMMPRIS led to better risk factor control during the study for almost all risk factors. Implementation of a lifestyle modification program in a vascular disease prevention clinical trial may improve risk factor outcomes.
Disclosures and Contributions Sami Al Kasab, MD, has no relationships or support to disclose. He participated in the conceptualization of this study, data interpretation, and writing of this manuscript. Michael J. Lynn, MS, reports funding from the National Institutes of Health—National Institute of Neurological Disorders and Stroke (NIH/NINDS) during the conduct of SAMMPRIS. He participated on the Executive Committee of Stenting Aggressive Medical Management for
T.N. TURAN ET AL.
Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) and in the conceptualization of SAMMPRIS and this study, statistical analysis of the data, and writing of this article. Tanya Turan, MD, reports funding from NIH/NINDS during the conduct of SAMMPRIS, a K23 grant from NIH/ NINDS unrelated to this project; other from CardioNet (consultant); personal fees from Gore and Boehringer Ingelheim for participating as a stroke adjudicator in clinical trials unrelated to this work; and personal fees as an Expert Witness in medical legal cases unrelated to this research. She participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. Colin Derdeyn, MD, reports funding from NIH/NINDS during the conduct of SAMMPRIS and has relationships with companies that manufacture medical devices for the treatment of cerebrovascular disease in general, although none directly involved in this study. These are W.L. Gore and Associates (Scientific Advisory Board and Consultant), Microvention, Inc. (Angiographic Core Lab for clinical trial); Penumbra, Inc. (Data and Safety Monitoring Board member for clinical trial); and Pulse Therapeutics (Chair, Scientific Advisory Board). He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. David Fiorella, MD, PhD, reports funding from NIH/ NINDS during the conduct of SAMMPRIS; research or salary support from Siemens, Microintervention, and Sequent; consulting fees from Covidien/Ev3, Codman & Shurtleff, and Penumbra; and royalties from Codman & Shurtleff (REVIVE). He has ownership and stock interests in Vascular Simulators LLC, TDC Technologies, and CVSL. He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. Bethany F. Lane, RN, reports funding from NIH/ NINDS during the conduct of SAMMPRIS. She participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, protocol compliance, data quality control, and editing of this article. L. Scott Janis, PhD, has no conflicts of interest to disclose. He participated on the Executive Committee of SAMMPRIS and editing of this article. Marc I. Chimowitz, MBChB, reports funding from NIH/ NINDS during the conduct of SAMMPRIS and other grants from NIH/NINDS related to the treatment of intracranial arterial stenosis. He also reports other support from Astra Zeneca and Stryker Neurovascular (formerly Boston Scientific Neurovascular) related to the SAMMPRIS trial. He also reports personal fees from Gore Associates, Merck/ Parexel, and Medtronic for participating as a stroke adjudicator or data safety monitoring board member on clinical trials unrelated to the submitted work. He also reports personal fees as an Expert Witness in medical legal
SAMMPRIS RISK FACTOR CONTROL AND LIFESTYLE MODIFICATION
cases related to stroke. He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS and this study, data analysis, and writing of this article. Acknowledgments: Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third-party device distribution, site monitoring, and study auditing. This research was also supported by the Investigator-Sponsored Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to study patients. INTERVENT provided the lifestyle modification program to the study at a discounted rate. The Regulatory and Clinical Research Institute (Minneapolis, MN) provided assistance in designing the site monitoring processes and perform the site monitoring visits. The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, NM) handled the procurement, labeling, distribution, and inventory management of the study devices and rosuvastatin. Walgreens Pharmacy provided study medications except rosuvastatin to patients at a discounted price (paid for by the study). The patient-centered assessment and counseling for exercise self-assessment forms for physical activity and smoking cessation were provided by the San Diego Center for Health Interventions, LLC.
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References 1. Turan TN, Lynn MJ, Nizam A, et al. Rationale, design, and implementation of aggressive risk factor management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis
10.
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(SAMMPRIS) trial. Circ Cardiovasc Qual Outcomes 2012;5:e51-e60. Derdeyn CP, Chimowitz MI, Lynn MJ, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2014; 383:333-341. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993-1003. Turan TN, Nizam A, Lynn MJ, et al. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology 2017;88:379-385. Lafranchise EF, Widener WG, Franklin BA, et al. Need for and clinical effectiveness of a neurologist supervised, nurse case managed stroke risk reduction program [abstract]. Stroke 2000;32:367. Gordon NF, Salmon RD, Franklin BA, et al. Effectiveness of therapeutic lifestyle changes in patients with hypertension, hyperlipidemia, and/or hyperglycemia. Am J Cardiol 2004;94:1558-1561. Gordon NF, English CD, Contractor AS, et al. Effectiveness of three models for comprehensive cardiovascular disease risk reduction. Am J Cardiol 2002;89:1263-1268. Chimowitz MI, Lynn MJ, Turan TN, et al. Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial. J Stroke Cerebrovasc Dis 2011;20:357-368. Daubenmier JJ, Weidner G, Sumner MD, et al. The contribution of changes in diet, exercise, and stress management to changes in coronary risk in women and men in the multisite cardiac lifestyle intervention program. Ann Behav Med 2007;33:57-68. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. NEJM 2005;353:2111-2120.
Background: Lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack and those with multiple risk factors. Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) was the first vascular disease prevention trial to provide a commercially available lifestyle modification program to enhance risk factor control. We sought to determine the relationship between compliance with this program and risk factor control in SAMMPRIS. Methods: SAMMPRIS aggressive medical management included a telephonic lifestyle modification program provided free of charge to all subjects (n = 451) during their participation in the study. Subjects with fewer than 3 expected lifestyle-coaching calls were excluded from these analyses. Compliant subjects (n = 201) had greater than or equal to 78.5% of calls (median % of completed/expected calls). Noncompliant subjects (n = 200) had less than 78.5% of calls or refused to participate. Mean risk factor values or % in-target for each risk factor was compared between compliant versus noncompliant subjects, using t tests and chi-square tests. Risk factor changes from baseline to follow-up were compared between the groups to account for baseline differences. Results: Compliant subjects had better risk factor control throughout follow-up for low-density lipoprotein, systolic blood pressure (SBP), hemoglobin A1c (HgA1c), non–high-density lipoprotein, nonsmoking, and
From the *Department of Neurology, Medical University of South Carolina, Charleston, South Carolina; †Department of Public Health, Emory University, Atlanta, Georgia; ‡Department of Radiology, University of Iowa, Iowa City, Iowa; §Department of Neurosurgery, State University of New York at Stony Brook, Stony Brook, New York; and ‖Division of Clinical Research, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland. Received July 26, 2017; accepted October 13, 2017. Grant support: This study was funded by a research grant (U01 NS058728) from the US Public Health Service National Institute of Neurological Disorders and Stroke. In addition, the following Clinical and Translational Science Awards, funded by the National Institutes of Health U01 NS058728, provided local support for the evaluation of patients in the trial: Medical University of South Carolina (UL1RR029882), University of Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and University of California, San Francisco (UL1RR024131). Address correspondence to Sami Al Kasab, MD, Department of Neurology, Medical University of South Carolina, 96 Jonathan Lucas St, Charleston, SC 29425. E-mail: [email protected]. 1052-3057/$ - see front matter Published by Elsevier Inc. on behalf of National Stroke Association. https://doi.org/10.1016/j.jstrokecerebrovasdis.2017.10.017
Journal of Stroke and Cerebrovascular Diseases, Vol. 27, No. 3 (March), 2018: pp 801–805
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T.N. TURAN ET AL.
802 exercise than noncompliant subjects, but there was no difference for body mass index. After adjusting for baseline differences between the groups, compliant subjects had a greater change from baseline than noncompliant subjects for SBP did at 24 months and HgA1c at 6 months. Conclusion: SAMMPRIS subjects who were compliant with the lifestyle modification program had better risk factor control during the study for almost all risk factors. Key Words: Stroke—intracranial atherosclerosis—medical management—compliance—lifestyle modification program. Published by Elsevier Inc. on behalf of National Stroke Association.
Introduction The Stenting Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) Trial was the first stroke prevention trial to employ protocol-driven multimodal aggressive management of multiple vascular risk factors, including elevated blood pressure, cholesterol, diabetes mellitus (DM), smoking, weight, and exercise. The results of the trial showed that aggressive medical management was superior to stenting for stroke prevention in patients with recently symptomatic severe intracranial stenosis,1-3 and that good risk factor control was associated with better outcomes.4 The SAMMPRIS Trial was also the first vascular disease prevention trial to incorporate a commercially available telephonic lifestyle modification program for study participants to enhance risk factor control. Although lifestyle modification programs have improved the achievement of risk factor targets in a variety of clinical settings, including patients who have previously suffered a stroke or transient ischemic attack,5-7 to our knowledge, such programs have not been evaluated in the setting of a vascular prevention clinical trial. In the present study, we sought to determine if utilization of a lifestyle modification program improved risk factor control in the setting of a clinical trial.
Methods The overall design of SAMMPRIS and its aggressive medical management protocols have been described previously.1,8 Funded by the National Institutes of Health, SAMMPRIS was an investigator-initiated and designed phase III randomized multicenter trial in which 451 patients were randomized at 50 sites in the United States. Institutional review boards at all 50 participating sites approved the study protocol. Aggressive medical therapy alone versus percutaneous transluminal angioplasty and stenting with the wingspan stent system plus aggressive medical therapy versus stenting plus aggressive medical therapy. Aggressive risk factor management primarily targeted systolic blood pressure (SBP) less than 140 mm Hg and low-density lipoprotein (LDL) less than 70 mg/dL. Secondary risk factors targeted included diabetes mellitus, physical inactivity, weight, and smoking. Using a commercially available lifestyle mod-
ification program (INTERVENT), all subjects received coaching on healthy lifestyle behaviors at regularly schedule times throughout the study at no charge. Lifestyle coaches provided individualized risk factor counseling (by telephone or Internet) twice a month for 6 months and monthly thereafter. For this analysis, subjects with fewer than 3 expected lifestyle-coaching calls (e.g., those who left the study early due to end point, or withdrew consent) were excluded. There was no prespecified definition of compliance. Therefore, subjects were considered “compliant” if they completed more than the mean percentage of expected calls or more. Subjects were considered “noncompliant” if they completed less than the mean percentage of expected calls or refused to participate in INTERVENT at all. Risk factor values for each subject during follow-up were recorded at baseline, 30 days, 4 months, and every 4 months thereafter. Mean risk factor values (SBP, LDL, non–high-density lipoprotein [HDL], hemoglobin A1c [HbA1c], body mass index [BMI]) or percent in-target (physical activity and smoking cessation) were compared between compliant and noncompliant subjects, using t tests and chi-square tests. To account for baseline differences between groups, risk factor changes from baseline to follow-up were also compared between the groups using t tests, Fisher’s exact tests, and chi-square tests.
Results The median percentage of expected calls that were completed by the subjects was 78.5%. Therefore, “compliant” subjects (n = 201) were defined as those who completed 78.5% or more expected calls from lifestyle coaches and “noncompliant” subjects (n = 200) completed less than 78.5% of calls or refused to participate at all. Baseline characteristics are summarized in Table 1. African-Americans were found to be less compliant with INTERVENT (9% compliant vs. 15% noncompliant) when compared to whites (38% compliant vs. 32% noncompliant) (P = .04). There was no significant difference with regard to compliance among assigned treatment groups (P = .29). As shown in Figure 1, compliant subjects had better control than noncompliant subjects of LDL, non-HDL, and HgA1c at baseline (P < .05). At several time points in the study follow-up period, compliant subjects also had better risk factor control than noncompliant subjects for
SAMMPRIS RISK FACTOR CONTROL AND LIFESTYLE MODIFICATION
Table 1. Comparison of baseline characteristics in the compliant and noncompliant treatment groups
Age (years) Race White AfricanAmerican Sex Male Female Treatment assignment Medical PTAS plus medical
Compliant (n = 201)
Non-compliant (n = 200)
60.7 (±10.8)
58.7 (±11.8)
154 (38%) 37 (9%)
128 (32%) 59 (15%)
P value .08* .04†
(48%) (53%)
P = .04), and the change in SBP from baseline to 24 months (−18.4 ± 21.6 mmHg, n = 171 vs. −11.2 ± 23.5 mmHg, n = 130; P = .006). Compliant and noncompliant subjects also differed in the change from baseline to 36 months for diastolic blood pressure (−6.2 ± 11.8 mmHg, n = 113 vs. −4.2 ± 12.5 mm Hg, n = 60; P = .02) and HDL (10.3 ± 14.9 mg/ dL, n = 55 vs. 1.6 ± 10.5 mg/dL, n = 17; P = .03).
Discussion .09‡
134 (33%) 67 (17%)
803
117 (30%) 83 (21%)
.29 ‡
Abbreviation: PTA, percutaneous transluminal angioplasty and stenting. *t Test. †Fisher’s exact test. ‡Chi-square P value.
LDL, SBP, HgA1c, non-HDL, non-smoking, and exercise (P < .05), but there was no difference for BMI. There was a significant difference between compliant and noncompliant subjects in the change in HbA1c from baseline to 6 months (−.7% ± 1.9%, n = 59 vs. .2% ± 2.7%, n = 58;
These post hoc analyses of patients in the SAMMPRIS Trial show that adherence to a lifestyle modification program was associated with significantly better control of almost all vascular risk factors. To our knowledge, this is the first study to evaluate the impact of incorporating a lifestyle modification program into a large secondary prevention vascular clinical trial and show that such programs can improve intensive risk factor control when used by clinical trial participants. Our results are consistent with a previous small cohort study of patients with stroke, transient ischemic attack, and carotid artery stenosis, which reported that active participation in lifestyle health coaching is associated with improved vascular risk factor control.5 Gordon et al also found that patients with conventional coronary heart disease risk factors could achieve risk factor control within 12 weeks of initiating therapeutic lifestyle changes without medications when supported by a community-based lifestyle management program.6 Another study, by Daubenmier et al, evaluated the impact
Figure 1. Risk factor control in compliant versus noncompliant subjects. Abbreviations: BMI, body mass index; HgA1c, hemoglobin A1c; LDL, lowdensity lipoprotein; non-HDL, non–high-density lipoprotein; SBP, systolic blood pressure.
804
of a health insurance-based Multisite Cardiac Lifestyle Intervention Program on changes in coronary risk and psychosocial factors at 3 months in 869 nonsmoking patients with cardiovascular heart disease.9 Daubenmier et al found that improvements in stress management, exercise, and dietary fat intake were significantly associated with improvements in coronary risk (reduction in weight, LDL, and increased exercise) and psychosocial factors. Although our findings suggest that compliance with the lifestyle modification program led to overall better risk factor control and better outcome, we cannot rule out the confounding possibility that patients who were noncompliant with INTERVENT were noncompliant in general (e.g., with medications) and would have worse risk factor control as a result; other research has suggested that lifestyle modification alone and without medications improves risk factor control. A study by Wadden et al compared the effect of lifestyle modification and pharmacotherapy for obesity.10 The investigators randomly assigned 224 obese adults to receive medical therapy alone, lifestyle modification alone, and pharmacotherapy in addition to lifestyle modification. The study showed that subjects receiving combined therapy lost 12.1 ± 7.4 kg; those treated with lifestyle modification alone lost 6.7 ± 7.9 kg; and those with pharmacotherapy alone lost 5.0 ± 7.4 kg. Additionally, the study discussed by Gordon et al showed that lifestyle modification alone without medical therapy can lead to vascular risk factor control at 12 weeks.6 Because we did not collect data on medication compliance, we cannot exclude this possibility. However, efforts to improve compliance with risk factor control in general (e.g., providing study medications to subjects at no cost and frequent follow-up visits) would be expected to minimize some common compliance issues.
Conclusion Compliance with the lifestyle modification program in SAMMPRIS led to better risk factor control during the study for almost all risk factors. Implementation of a lifestyle modification program in a vascular disease prevention clinical trial may improve risk factor outcomes.
Disclosures and Contributions Sami Al Kasab, MD, has no relationships or support to disclose. He participated in the conceptualization of this study, data interpretation, and writing of this manuscript. Michael J. Lynn, MS, reports funding from the National Institutes of Health—National Institute of Neurological Disorders and Stroke (NIH/NINDS) during the conduct of SAMMPRIS. He participated on the Executive Committee of Stenting Aggressive Medical Management for
T.N. TURAN ET AL.
Prevention of Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) and in the conceptualization of SAMMPRIS and this study, statistical analysis of the data, and writing of this article. Tanya Turan, MD, reports funding from NIH/NINDS during the conduct of SAMMPRIS, a K23 grant from NIH/ NINDS unrelated to this project; other from CardioNet (consultant); personal fees from Gore and Boehringer Ingelheim for participating as a stroke adjudicator in clinical trials unrelated to this work; and personal fees as an Expert Witness in medical legal cases unrelated to this research. She participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. Colin Derdeyn, MD, reports funding from NIH/NINDS during the conduct of SAMMPRIS and has relationships with companies that manufacture medical devices for the treatment of cerebrovascular disease in general, although none directly involved in this study. These are W.L. Gore and Associates (Scientific Advisory Board and Consultant), Microvention, Inc. (Angiographic Core Lab for clinical trial); Penumbra, Inc. (Data and Safety Monitoring Board member for clinical trial); and Pulse Therapeutics (Chair, Scientific Advisory Board). He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. David Fiorella, MD, PhD, reports funding from NIH/ NINDS during the conduct of SAMMPRIS; research or salary support from Siemens, Microintervention, and Sequent; consulting fees from Covidien/Ev3, Codman & Shurtleff, and Penumbra; and royalties from Codman & Shurtleff (REVIVE). He has ownership and stock interests in Vascular Simulators LLC, TDC Technologies, and CVSL. He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, data analysis, and editing of this article. Bethany F. Lane, RN, reports funding from NIH/ NINDS during the conduct of SAMMPRIS. She participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS, protocol compliance, data quality control, and editing of this article. L. Scott Janis, PhD, has no conflicts of interest to disclose. He participated on the Executive Committee of SAMMPRIS and editing of this article. Marc I. Chimowitz, MBChB, reports funding from NIH/ NINDS during the conduct of SAMMPRIS and other grants from NIH/NINDS related to the treatment of intracranial arterial stenosis. He also reports other support from Astra Zeneca and Stryker Neurovascular (formerly Boston Scientific Neurovascular) related to the SAMMPRIS trial. He also reports personal fees from Gore Associates, Merck/ Parexel, and Medtronic for participating as a stroke adjudicator or data safety monitoring board member on clinical trials unrelated to the submitted work. He also reports personal fees as an Expert Witness in medical legal
SAMMPRIS RISK FACTOR CONTROL AND LIFESTYLE MODIFICATION
cases related to stroke. He participated on the Executive Committee of SAMMPRIS and in the conceptualization of SAMMPRIS and this study, data analysis, and writing of this article. Acknowledgments: Stryker Neurovascular (formerly Boston Scientific Neurovascular) provided study devices and supplemental funding for third-party device distribution, site monitoring, and study auditing. This research was also supported by the Investigator-Sponsored Study Program of AstraZeneca, which donated rosuvastatin (Crestor) to study patients. INTERVENT provided the lifestyle modification program to the study at a discounted rate. The Regulatory and Clinical Research Institute (Minneapolis, MN) provided assistance in designing the site monitoring processes and perform the site monitoring visits. The VA Cooperative Studies Program Clinical Research Pharmacy Coordinating Center (Albuquerque, NM) handled the procurement, labeling, distribution, and inventory management of the study devices and rosuvastatin. Walgreens Pharmacy provided study medications except rosuvastatin to patients at a discounted price (paid for by the study). The patient-centered assessment and counseling for exercise self-assessment forms for physical activity and smoking cessation were provided by the San Diego Center for Health Interventions, LLC.
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References 1. Turan TN, Lynn MJ, Nizam A, et al. Rationale, design, and implementation of aggressive risk factor management in the Stenting and Aggressive Medical Management for Prevention of Recurrent Stroke in Intracranial Stenosis
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(SAMMPRIS) trial. Circ Cardiovasc Qual Outcomes 2012;5:e51-e60. Derdeyn CP, Chimowitz MI, Lynn MJ, et al. Aggressive medical treatment with or without stenting in high-risk patients with intracranial artery stenosis (SAMMPRIS): the final results of a randomised trial. Lancet 2014; 383:333-341. Chimowitz MI, Lynn MJ, Derdeyn CP, et al. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl J Med 2011;365:993-1003. Turan TN, Nizam A, Lynn MJ, et al. Relationship between risk factor control and vascular events in the SAMMPRIS trial. Neurology 2017;88:379-385. Lafranchise EF, Widener WG, Franklin BA, et al. Need for and clinical effectiveness of a neurologist supervised, nurse case managed stroke risk reduction program [abstract]. Stroke 2000;32:367. Gordon NF, Salmon RD, Franklin BA, et al. Effectiveness of therapeutic lifestyle changes in patients with hypertension, hyperlipidemia, and/or hyperglycemia. Am J Cardiol 2004;94:1558-1561. Gordon NF, English CD, Contractor AS, et al. Effectiveness of three models for comprehensive cardiovascular disease risk reduction. Am J Cardiol 2002;89:1263-1268. Chimowitz MI, Lynn MJ, Turan TN, et al. Design of the stenting and aggressive medical management for preventing recurrent stroke in intracranial stenosis trial. J Stroke Cerebrovasc Dis 2011;20:357-368. Daubenmier JJ, Weidner G, Sumner MD, et al. The contribution of changes in diet, exercise, and stress management to changes in coronary risk in women and men in the multisite cardiac lifestyle intervention program. Ann Behav Med 2007;33:57-68. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. NEJM 2005;353:2111-2120.