- Email: [email protected]
VALPROATE ATTENUATES THE RISK OF MYOCARDIAL INFARCTION IN PATIENTS WITH EPILEPSY: A NATIONWIDE COHORT STUDY
A54.E516 JACC March 9, 2010 Volume 55, issue 10A
HYPERTENSION, LIPIDS AND PREVENTION VALPROATE ATTENUATES THE RISK OF MYOCARDIAL INFARCTION IN PATIENTS WITH EPILEPSY: A NATIONWIDE COHORT STUDY ACC Poster Contributions Georgia World Congress Center, Hall B5 Monday, March 15, 2010, 9:30 a.m.-10:30 a.m.
Session Title: Clinical Trials and Interventional Therapies Abstract Category: Risk Reduction and Rehabilitation Presentation Number: 1127-90 Authors: Jonas B. Olesen, Peter R. Hansen, Steen Z. Abildstrøm, Charlotte Andersson, Peter Weeke, Michelle Schmiegelow, Jesper Erdal, Christian Torp-Pedersen, Gunnar H. Gislason, Gentofte University Hospital, Copenhagen, Denmark Background: Patients with epilepsy have an increased risk of myocardial infarction (MI). Experimental studies have suggested that valproate may inhibit atherosclerosis. In this study, we investigated the risk of MI and all-cause death associated with valproate-treated epilepsy compared to matched controls. Methods: Cases with valproate-treated epilepsy were identified by individual-level-linkage of nationwide registers and matched with 10 controls from the general Danish population. The cohort was followed in the period 1997-2006. Hazard ratios (HRs) for MI and all-cause death were estimated by multivariable Cox proportional-hazard models, including valproate exposure as a time-dependent covariate. Results: The cohort comprised 9273 cases and 92,730 controls, 3320 subjects experienced an MI in the study period and 22,774 died. Multivariate Cox regression analyses demonstrated a decreased risk of MI and a neutral risk of all-cause death with valproate-treated epilepsy. The HR for MI with valproate-treated epilepsy fell successively with step-wise adjustments for sex, age, year of study inclusion, previous MI and stroke, concomitant pharmacotherapy, comorbidity, and civil status (Table 1). Conclusion: Valproate treatment markedly diminished the risk of MI in this nationwide cohort of patients with epilepsy, compared to controls. Effects of valproate on the risk of MI in patients with epilepsy warrant further prospective investigations. Table 1. Hazard ratios in patients with valproate-treated epilepsy Myocardial infarction All-cause death HR (CI) P value HR (CI) P value Valproate-treated 0.80 (0.69-0.93) 0.003 1.46 (1.40-1.53) <0.0001 epilepsy* Valproate-treated 0.66 (0.56-0.77) <0.0001 1.21 (1.15-1.27) <0.0001 epilepsy† Valproate-treated 0.62 (0.53-0.73) <0.0001 1.02 (0.97-1.07) 0.41 epilepsy‡ Results of Cox proportional-hazard models. The reference was 1:10 sex- and age matched controls from the Danish population. HR: Hazard ratio; CI: 95% confidence limits. * Adjusted for sex, age, and year of study inclusion † Adjusted for the above, previous myocardial infarction, and previous stroke ‡ Adjusted for the above, concomitant pharmacotherapy, Charlson comorbidity index score, and civil status
HYPERTENSION, LIPIDS AND PREVENTION VALPROATE ATTENUATES THE RISK OF MYOCARDIAL INFARCTION IN PATIENTS WITH EPILEPSY: A NATIONWIDE COHORT STUDY ACC Poster Contributions Georgia World Congress Center, Hall B5 Monday, March 15, 2010, 9:30 a.m.-10:30 a.m.
Session Title: Clinical Trials and Interventional Therapies Abstract Category: Risk Reduction and Rehabilitation Presentation Number: 1127-90 Authors: Jonas B. Olesen, Peter R. Hansen, Steen Z. Abildstrøm, Charlotte Andersson, Peter Weeke, Michelle Schmiegelow, Jesper Erdal, Christian Torp-Pedersen, Gunnar H. Gislason, Gentofte University Hospital, Copenhagen, Denmark Background: Patients with epilepsy have an increased risk of myocardial infarction (MI). Experimental studies have suggested that valproate may inhibit atherosclerosis. In this study, we investigated the risk of MI and all-cause death associated with valproate-treated epilepsy compared to matched controls. Methods: Cases with valproate-treated epilepsy were identified by individual-level-linkage of nationwide registers and matched with 10 controls from the general Danish population. The cohort was followed in the period 1997-2006. Hazard ratios (HRs) for MI and all-cause death were estimated by multivariable Cox proportional-hazard models, including valproate exposure as a time-dependent covariate. Results: The cohort comprised 9273 cases and 92,730 controls, 3320 subjects experienced an MI in the study period and 22,774 died. Multivariate Cox regression analyses demonstrated a decreased risk of MI and a neutral risk of all-cause death with valproate-treated epilepsy. The HR for MI with valproate-treated epilepsy fell successively with step-wise adjustments for sex, age, year of study inclusion, previous MI and stroke, concomitant pharmacotherapy, comorbidity, and civil status (Table 1). Conclusion: Valproate treatment markedly diminished the risk of MI in this nationwide cohort of patients with epilepsy, compared to controls. Effects of valproate on the risk of MI in patients with epilepsy warrant further prospective investigations. Table 1. Hazard ratios in patients with valproate-treated epilepsy Myocardial infarction All-cause death HR (CI) P value HR (CI) P value Valproate-treated 0.80 (0.69-0.93) 0.003 1.46 (1.40-1.53) <0.0001 epilepsy* Valproate-treated 0.66 (0.56-0.77) <0.0001 1.21 (1.15-1.27) <0.0001 epilepsy† Valproate-treated 0.62 (0.53-0.73) <0.0001 1.02 (0.97-1.07) 0.41 epilepsy‡ Results of Cox proportional-hazard models. The reference was 1:10 sex- and age matched controls from the Danish population. HR: Hazard ratio; CI: 95% confidence limits. * Adjusted for sex, age, and year of study inclusion † Adjusted for the above, previous myocardial infarction, and previous stroke ‡ Adjusted for the above, concomitant pharmacotherapy, Charlson comorbidity index score, and civil status