Objectives: In a previous study about severe hypoglycemic coma events (SH) among diabetes mellitu... more Objectives: In a previous study about severe hypoglycemic coma events (SH) among diabetes mellitus (DM) patients we saw regional variation in SH occurrence. The purpose was to compare the incidence of SH between hospital districts in Finland. MethOds: This study among type 1 (T1) and 2 (T2) diabetic patients was based on nationwide health care registers. The study cohort contained insulin naïve diabetic patients who had filled at least one prescription of insulin during follow-up in 2006-2009. SH was defined as a hospitalization or a secondary health care visit due to hypoglycemic coma (ICD-10: E10.00 and E11.00). Stratified incidence rates and adjusted hazard ratio (HR) estimates with 95% confidence intervals (CI) were calculated. Analyses were performed for the first and recurrent SHs. Results: The population comprised 5271 (17.6%) patients with T1 and 24602 (82.4%) with T2. Altogether 3.1% patients experienced at least one SH during the follow-up. In different hospital districts the rate of first SHs varied from 5.6 (Varsinais-Suomi) to 47.8 (Länsi-Pohja) for T1, and from 4.8 (Pohjois-Karjala) to 50.3 (Länsi-Pohja) for T2. Compared to the capital area, the risks of first SHs varied differently for T1 and T2, but were commonly higher in Länsi-Pohja (T1: HR 3.46, CI 1.41-8.46; T2: HR 1.60, CI 1.13-2.29) and lower in Pohjois-Karjala (T1: no events; T2: HR 0.275, CI 0.14-0.56). Taking all SH events into account did not change these differences remarkably. cOnclusiOns: We found differences between regions in risk of hospital-treated SH in both DM types. Further analyses will be performed for e. g. ambulance density.
Background Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–G... more Background Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). Methods and results Adults initiating empagliflozin and DPP-4i in 2014–2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-poin...
Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insu... more Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†
We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patient... more We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice.
Background Randomized, controlled cardiovascular outcome trials may not be fully representative o... more Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple ...
A central problem in pattern recognition is the classi cation of a feature vector into one of sev... more A central problem in pattern recognition is the classi cation of a feature vector into one of several possible classes. In polychotomous classi cation the number of possible classes is higher than two. Given a set of training vectors with known classes, a classi er can be constructed using for example some density estimation or regression method. In a typical approach one estimates, using all training data from all classes, the posterior probability functions of each class and then classi es future feature vectors according to the highest estimated posterior probability. In some recent proposals a di erent approach is suggested where one rst estimates classi ers only for each pair of classes and then combines these into a nal polychotomous classi er (Friedman 1996, Hastie and Tibshirani 1998). The advantages of the pairwise approach are hoped to come from both increased classi cation accuracy and reduction in computational complexity. We report experimental results using various cla...
The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontin... more The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontinue postmenopausal hormone therapy (HT). We analyzed the risk of death due to cardiac (n = 5,204) and cerebrovascular (n = 3,434) causes in Finnish women who discontinued systemic HT during 1994 to 2013 (n = 432,775). The risks were compared with those in the age-matched female background population and with those in age-matched HT users. Women diagnosed with cardiac or cerebrovascular events within 1 year before discontinuation of HT were excluded (n = 8,711). Women younger than 60 years at discontinuation of HT showed a significantly increased risk of cardiac death (after ≤5 y of HT exposure, standardized mortality ratio [SMR] 1.52, 95% CI 1.13-2.00; after >5 y of exposure, SMR 2.08, 95% CI 1.44-2.90) and stroke death (after ≤5 y of exposure, SMR 2.62, 95% CI 2.07-3.28; after >5 y of exposure, SMR 3.22, 95% CI 2.29-4.40) during the first year after treatment as compared with age-m...
It has remained controversial if antipsychotic treatment is associated with increased or decrease... more It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. We linked prospectively gathered nationwide register-based data during 2006-2013 to study all-cause mortality among all patients aged 16-64years with schizophrenia in Sweden (N=29,823 in total; N=4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. During the mean follow-up of 5.7years, 2515 patients (8.4%) died. During the maximum follow-up (7.5years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01-1.86) for first generation (FG) LAIs, ...
Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lit... more Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations. To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder. This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was us...
The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinenc... more The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI. The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis. The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxypr...
The Journal of Clinical Endocrinology & Metabolism, 2016
There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dement... more There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dementia (VD) and Alzheimer's disease (AD). Objective: We analyzed the mortality risk attributable to VD or AD in women with a history of HT use.
Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mort... more Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT). In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population. The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality. In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.
The Journal of clinical endocrinology and metabolism, Jul 12, 2016
The "window of opportunity hypothesis" refers to data indicating that conjugated equine... more The "window of opportunity hypothesis" refers to data indicating that conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, if initiated before 60 years of age, protects the heart but endangers it if initiated later (Women's Health Initiative study). Less is known about the "window of opportunity hypothesis" with natural estradiol alone (ET) or with various progestins in combination with estradiol (EPT). We related the death risk from coronary heart disease (CHD) in users of ET or EPT to the age at the initiation of therapy and to the progestin component of EPT. Design, Patients, Interventions, and Main Outcome Measures: Altogether, 498ü105 women had used ET or EPT containing medroxyprogesterone, norethisterone acetate, dydrogesterone, other progestins, or tibolone during 3.7 million person-years during 1994-2009. Women were followed from the therapy initiation to death, or to the end of year 2009. The risk of CHD death in hormo...
The Journal of Clinical Endocrinology & Metabolism, 2015
Context: Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (H... more Context: Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (HT) to evaluate whether a woman could manage without the treatment. The impact of HT on cardiovascular health has been widely studied, but it is not known how withdrawal of HT affects cardiovascular risk. Objective: We evaluated the risk of cardiac or stroke death after the discontinuation of HT. Altogether 332 202 Finnish women discontinuing HT between 1994 -2009 (data from National Reimbursement register) were followed from the discontinuation date to death due to cardiac cause (nϭ3 177) or stroke (nϭ1 952), or to the end of 2009. The deaths, retrieved from the national Cause of Death Register, were compared with the expected number of deaths in the age-standardized background population. In a subanalysis we also compared HT stoppers with HT users. Results: Within the first post-treatment year, the risk of cardiac death was significantly elevated (standardized mortality ratio; 95% confidence interval 1.26; 1.16 -1.37), whereas follow-up Ͼ1 year was accompanied with reduction (0.75; 0.72-0.78). The risk of stroke death in the first posttreatment year was increased (1.63; 1.47-1.79), but follow-up Ͼ1 year accompanied with a reduced risk (0.89; 0.85-0.94). The cardiac (2.30; 2.12-2.50) and stroke (2.52; 2.28 -2.77) death risk elevations were even higher when compared to HT users. In women who discontinued HT at Ͻ60, but not in women aged Ն60 years, cardiac mortality risk was elevated (1.94; 1.51-2.48). Increased cardiovascular death risks question the safety of annual HT discontinuation practice to evaluate whether a woman could manage without HT.
Objectives: In a previous study about severe hypoglycemic coma events (SH) among diabetes mellitu... more Objectives: In a previous study about severe hypoglycemic coma events (SH) among diabetes mellitus (DM) patients we saw regional variation in SH occurrence. The purpose was to compare the incidence of SH between hospital districts in Finland. MethOds: This study among type 1 (T1) and 2 (T2) diabetic patients was based on nationwide health care registers. The study cohort contained insulin naïve diabetic patients who had filled at least one prescription of insulin during follow-up in 2006-2009. SH was defined as a hospitalization or a secondary health care visit due to hypoglycemic coma (ICD-10: E10.00 and E11.00). Stratified incidence rates and adjusted hazard ratio (HR) estimates with 95% confidence intervals (CI) were calculated. Analyses were performed for the first and recurrent SHs. Results: The population comprised 5271 (17.6%) patients with T1 and 24602 (82.4%) with T2. Altogether 3.1% patients experienced at least one SH during the follow-up. In different hospital districts the rate of first SHs varied from 5.6 (Varsinais-Suomi) to 47.8 (Länsi-Pohja) for T1, and from 4.8 (Pohjois-Karjala) to 50.3 (Länsi-Pohja) for T2. Compared to the capital area, the risks of first SHs varied differently for T1 and T2, but were commonly higher in Länsi-Pohja (T1: HR 3.46, CI 1.41-8.46; T2: HR 1.60, CI 1.13-2.29) and lower in Pohjois-Karjala (T1: no events; T2: HR 0.275, CI 0.14-0.56). Taking all SH events into account did not change these differences remarkably. cOnclusiOns: We found differences between regions in risk of hospital-treated SH in both DM types. Further analyses will be performed for e. g. ambulance density.
Background Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–G... more Background Studies that have reported lower risk for cardiovascular outcomes in users of Sodium–Glucose Cotransporter-2 Inhibitors (SGLT-2i) are limited by residual cofounding and lack of information on prior cardiovascular disease (CVD). This study compared risk of cardiovascular events in patients within routine care settings in Europe and Asia with type 2 diabetes (T2D) initiating empagliflozin compared to dipeptidyl peptidase-4 inhibitors (DPP-4i) stratified by pre-existing CVD and history of heart failure (HF). Methods and results Adults initiating empagliflozin and DPP-4i in 2014–2018/19 from 11 countries in Europe and Asia were compared using propensity score matching and Cox proportional hazards regression to assess differences in rates of primary outcomes: hospitalisation for heart failure (HHF), myocardial infarction (MI), stroke; and secondary outcomes: cardiovascular mortality (CVM), coronary revascularisation procedure, composite outcome including HHF or CVM, and 3-poin...
Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insu... more Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study†
We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patient... more We examined safety outcomes of interest (SOI) and overall survival (OS) among lung cancer patients initiating crizotinib and erlotinib in routine clinical practice.
Background Randomized, controlled cardiovascular outcome trials may not be fully representative o... more Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple ...
A central problem in pattern recognition is the classi cation of a feature vector into one of sev... more A central problem in pattern recognition is the classi cation of a feature vector into one of several possible classes. In polychotomous classi cation the number of possible classes is higher than two. Given a set of training vectors with known classes, a classi er can be constructed using for example some density estimation or regression method. In a typical approach one estimates, using all training data from all classes, the posterior probability functions of each class and then classi es future feature vectors according to the highest estimated posterior probability. In some recent proposals a di erent approach is suggested where one rst estimates classi ers only for each pair of classes and then combines these into a nal polychotomous classi er (Friedman 1996, Hastie and Tibshirani 1998). The advantages of the pairwise approach are hoped to come from both increased classi cation accuracy and reduction in computational complexity. We report experimental results using various cla...
The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontin... more The aim of the study was to evaluate the risk of cardiac and stroke deaths in women who discontinue postmenopausal hormone therapy (HT). We analyzed the risk of death due to cardiac (n = 5,204) and cerebrovascular (n = 3,434) causes in Finnish women who discontinued systemic HT during 1994 to 2013 (n = 432,775). The risks were compared with those in the age-matched female background population and with those in age-matched HT users. Women diagnosed with cardiac or cerebrovascular events within 1 year before discontinuation of HT were excluded (n = 8,711). Women younger than 60 years at discontinuation of HT showed a significantly increased risk of cardiac death (after ≤5 y of HT exposure, standardized mortality ratio [SMR] 1.52, 95% CI 1.13-2.00; after >5 y of exposure, SMR 2.08, 95% CI 1.44-2.90) and stroke death (after ≤5 y of exposure, SMR 2.62, 95% CI 2.07-3.28; after >5 y of exposure, SMR 3.22, 95% CI 2.29-4.40) during the first year after treatment as compared with age-m...
It has remained controversial if antipsychotic treatment is associated with increased or decrease... more It has remained controversial if antipsychotic treatment is associated with increased or decreased mortality among patients with schizophrenia, and if there are any clinically meaningful differences between specific agents and routes of administration. We linked prospectively gathered nationwide register-based data during 2006-2013 to study all-cause mortality among all patients aged 16-64years with schizophrenia in Sweden (N=29,823 in total; N=4603 in the incident cohort). Multivariate Cox regression models were adjusted for clinical and sociodemographic covariates. Sensitivity analyses with the incident cohort were conducted to control for survival bias. During the mean follow-up of 5.7years, 2515 patients (8.4%) died. During the maximum follow-up (7.5years), the lowest cumulative mortality was observed for second generation (SG) long-acting injection (LAI) use (7.5%). Adjusted hazard ratios (aHRs) compared to SG LAI use were 1.37 (95%CI 1.01-1.86) for first generation (FG) LAIs, ...
Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lit... more Mood stabilizers and antipsychotics are the main maintenance treatments for bipolar disorder. Lithium is considered to be the most effective mood stabilizer, but very little is known about overall health outcomes associated with specific treatments and the comparative long-term effectiveness of specific psychotropics or routes of administration in the prevention of rehospitalizations. To study the comparative effectiveness of pharmacologic treatments in the prevention of rehospitalization in a nationwide cohort of patients with bipolar disorder. This cohort study examined the risk of psychiatric, cardiovascular, and all-cause hospitalization from January 1, 1987, to December 31, 2012, among all patients in Finland who had been hospitalized for bipolar disorder (N = 18 018; mean follow-up time, 7.2 years) using prospectively gathered nationwide databases for hospitalization and dispensed medications. The primary analysis was within-individual analysis, in which each individual was us...
The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinenc... more The impact of estradiol-based hormone therapy (HT) on the incidence of stress urinary incontinence (SUI) is unknown. Therefore, we compared the use of such HT regimens and tibolone in women with and without SUI. The women with a history of SUI operation (N = 15,002) were identified from the Finnish National Hospital Discharge Register, and the control women without such an operation (N = 44,389) from the Finnish Central Population Register. The use of HT was traced from the National Drug Reimbursement Register, and the odd ratios (ORs) with 95% confidence intervals (95% CIs) for SUI were calculated by using the conditional logistic regression analysis. The cases had used any HT more often than the controls. The use of systemic estradiol-only or estradiol-progestin therapy was accompanied by an increased SUI risk (OR 3.8, 95% CI: 3.6-4.0 and OR 2.7, 95% CI: 2.6-2.9 respectively). The use of estradiol with noretisterone acetate showed a higher risk of increase than that with medroxypr...
The Journal of Clinical Endocrinology & Metabolism, 2016
There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dement... more There are conflicting data on postmenopausal hormone therapy (HT) and the risk of vascular dementia (VD) and Alzheimer's disease (AD). Objective: We analyzed the mortality risk attributable to VD or AD in women with a history of HT use.
Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mort... more Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT). In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population. The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality. In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.
The Journal of clinical endocrinology and metabolism, Jul 12, 2016
The "window of opportunity hypothesis" refers to data indicating that conjugated equine... more The "window of opportunity hypothesis" refers to data indicating that conjugated equine estrogen alone or in combination with medroxyprogesterone acetate, if initiated before 60 years of age, protects the heart but endangers it if initiated later (Women's Health Initiative study). Less is known about the "window of opportunity hypothesis" with natural estradiol alone (ET) or with various progestins in combination with estradiol (EPT). We related the death risk from coronary heart disease (CHD) in users of ET or EPT to the age at the initiation of therapy and to the progestin component of EPT. Design, Patients, Interventions, and Main Outcome Measures: Altogether, 498ü105 women had used ET or EPT containing medroxyprogesterone, norethisterone acetate, dydrogesterone, other progestins, or tibolone during 3.7 million person-years during 1994-2009. Women were followed from the therapy initiation to death, or to the end of year 2009. The risk of CHD death in hormo...
The Journal of Clinical Endocrinology & Metabolism, 2015
Context: Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (H... more Context: Current guidelines recommend annual discontinuation of postmenopausal hormone therapy (HT) to evaluate whether a woman could manage without the treatment. The impact of HT on cardiovascular health has been widely studied, but it is not known how withdrawal of HT affects cardiovascular risk. Objective: We evaluated the risk of cardiac or stroke death after the discontinuation of HT. Altogether 332 202 Finnish women discontinuing HT between 1994 -2009 (data from National Reimbursement register) were followed from the discontinuation date to death due to cardiac cause (nϭ3 177) or stroke (nϭ1 952), or to the end of 2009. The deaths, retrieved from the national Cause of Death Register, were compared with the expected number of deaths in the age-standardized background population. In a subanalysis we also compared HT stoppers with HT users. Results: Within the first post-treatment year, the risk of cardiac death was significantly elevated (standardized mortality ratio; 95% confidence interval 1.26; 1.16 -1.37), whereas follow-up Ͼ1 year was accompanied with reduction (0.75; 0.72-0.78). The risk of stroke death in the first posttreatment year was increased (1.63; 1.47-1.79), but follow-up Ͼ1 year accompanied with a reduced risk (0.89; 0.85-0.94). The cardiac (2.30; 2.12-2.50) and stroke (2.52; 2.28 -2.77) death risk elevations were even higher when compared to HT users. In women who discontinued HT at Ͻ60, but not in women aged Ն60 years, cardiac mortality risk was elevated (1.94; 1.51-2.48). Increased cardiovascular death risks question the safety of annual HT discontinuation practice to evaluate whether a woman could manage without HT.
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