Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database

Alireza Aminsharifi, Lauren E. Howard, Christopher Amling, William J. Aronson, Matthew R. Cooperberg, Christopher J. Kane, Martha K. Terris, Thomas J. Polascik, Stephen J. Freedland

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Abstract

Purpose: To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men. Patients and Methods: Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c). Results: A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P =.003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c. Conclusion: Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations. We assessed the association between preoperative use of metformin and statin, alone or in combination, with biochemical recurrence (BCR) after radical prostatectomy (RP) in 843 men with diabetes. We also tested whether these associations varied as a function of race and/or body mass index (BMI). Preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin.

Original languageEnglish (US)
JournalClinical Genitourinary Cancer
DOIs
StateAccepted/In press - Jan 1 2018

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Metformin
Prostatectomy
Databases
Recurrence
Body Mass Index
Confidence Intervals
Pharmaceutical Preparations
Glycosylated Hemoglobin A
Proportional Hazards Models
Survival Rate

Keywords

  • Combination therapy
  • Diabetes
  • Metformin
  • Outcomes
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

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Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin : Results From the SEARCH Database. / Aminsharifi, Alireza; Howard, Lauren E.; Amling, Christopher; Aronson, William J.; Cooperberg, Matthew R.; Kane, Christopher J.; Terris, Martha K.; Polascik, Thomas J.; Freedland, Stephen J.

In: Clinical Genitourinary Cancer, 01.01.2018.

Research output: Contribution to journalArticle

Aminsharifi, Alireza ; Howard, Lauren E. ; Amling, Christopher ; Aronson, William J. ; Cooperberg, Matthew R. ; Kane, Christopher J. ; Terris, Martha K. ; Polascik, Thomas J. ; Freedland, Stephen J. / Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin : Results From the SEARCH Database. In: Clinical Genitourinary Cancer. 2018.
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title = "Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database",
abstract = "Purpose: To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men. Patients and Methods: Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c). Results: A total of 259 men (31{\%}) received statin therapy, 94 (11{\%}) metformin, 307 (36{\%}) metformin + statin, and 183 (22{\%}) neither. Five-year BCR-free survival rates were 75{\%} in metformin only versus 75{\%} in metformin + statin versus 60{\%} in statin versus 68{\%} in no drug groups (log-rank, P =.003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95{\%} confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95{\%} CI, 0.53-1.47) and metformin + statin (HR 0.88; 95{\%} CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95{\%} CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c. Conclusion: Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations. We assessed the association between preoperative use of metformin and statin, alone or in combination, with biochemical recurrence (BCR) after radical prostatectomy (RP) in 843 men with diabetes. We also tested whether these associations varied as a function of race and/or body mass index (BMI). Preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin.",
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author = "Alireza Aminsharifi and Howard, {Lauren E.} and Christopher Amling and Aronson, {William J.} and Cooperberg, {Matthew R.} and Kane, {Christopher J.} and Terris, {Martha K.} and Polascik, {Thomas J.} and Freedland, {Stephen J.}",
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T1 - Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin

T2 - Results From the SEARCH Database

AU - Aminsharifi, Alireza

AU - Howard, Lauren E.

AU - Amling, Christopher

AU - Aronson, William J.

AU - Cooperberg, Matthew R.

AU - Kane, Christopher J.

AU - Terris, Martha K.

AU - Polascik, Thomas J.

AU - Freedland, Stephen J.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Purpose: To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men. Patients and Methods: Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c). Results: A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P =.003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c. Conclusion: Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations. We assessed the association between preoperative use of metformin and statin, alone or in combination, with biochemical recurrence (BCR) after radical prostatectomy (RP) in 843 men with diabetes. We also tested whether these associations varied as a function of race and/or body mass index (BMI). Preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin.

AB - Purpose: To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men. Patients and Methods: Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c). Results: A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P =.003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m2 (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c. Conclusion: Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations. We assessed the association between preoperative use of metformin and statin, alone or in combination, with biochemical recurrence (BCR) after radical prostatectomy (RP) in 843 men with diabetes. We also tested whether these associations varied as a function of race and/or body mass index (BMI). Preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin.

KW - Combination therapy

KW - Diabetes

KW - Metformin

KW - Outcomes

KW - Prostate cancer

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