Initiation of statins and risk of venous thromboembolism: Population-based matched cohort study.

BACKGROUND: The effects of statins in prevention of venous thromboembolism (VTE) is not well established. OBJECTIVES: To examine the risks of first-time VTE in a cohort of patients initiating statin treatment and in a matched general population comparison cohort. METHODS: We conducted a nationwide, population-based, matched cohort study based on data from Danish health registries. The study period was 1 January 2005-31 December 2015. We identified statin initiators (without VTE, myocardial infarction, or ischemic stroke) and sex-, age-, and calendar year-matched (1,3) individuals from the general population (without statin use, VTE, myocardial infarction, or ischemic stroke). We computed cumulative risks and comorbidity-adjusted hazard ratios (HRs) of VTE, myocardial infarction, and ischemic stroke. RESULTS: Among 601,011 statin initiators and 1,803,033 matched population cohort members during 2005-2015, the cumulative risk after 11 years was 2.8% for VTE (both cohorts), 4.7% vs. 2.9% for myocardial infarction, and 7.1% vs. 5.2 for ischemic stroke. After adjustment, statin use was associated with a slightly decreased risk of VTE (adjusted HR: 0.95 [95% CI: 0.92-0.97]), driven by a reduced risk of unprovoked VTE (adjusted HR: 0.92 [95% CI: 0.89-0.95]). The reduced risks of VTE were more pronounced among patients who had an imaging examination performed. The adjusted HRs were elevated for myocardial infarction and ischemic stroke. CONCLUSION: Statin initiation was associated with a reduced risk of VTE, with no indication of a healthy-user effect. Based on available evidence, statins have weak thromboprophylactic effects.

Pregnancy, Birth, Neonatal, and Postnatal Neurological Outcomes After Pregnancy With Migraine.

BACKGROUND: Prevalence of migraine is high during the reproductive age. Although migraine often improves during pregnancy, the risk of adverse pregnancy, birth, neonatal, and neurological outcomes in mother and offspring remains poorly understood. OBJECTIVE: To investigate the associations between maternal migraine and risks of adverse pregnancy outcomes in the mother, and birth, neonatal and postnatal outcomes in the offspring. METHODS: We used Danish population registries to assemble a cohort of pregnancies among women with migraine and an age- and conception year-matched comparison cohort of pregnancies among women without migraine. The study period was 2005-2012. We computed adjusted prevalence ratios (aPRs) for pregnancy and birth outcomes and adjusted risk ratios (aRRs) for neonatal and postnatal outcomes, adjusting for age, preconception medical history, and preconception reproductive history. RESULTS: We identified 22,841 pregnancies among women with migraine and 228,324 matched pregnancies among women without migraine. Migraine was associated with an increased risk of pregnancy-associated hypertension disorders (aPR: 1.50 [95% confidence interval (CI): 1.39-1.61]) and miscarriage (aPR: 1.10 [95% CI: 1.05-1.15]). Migraine was associated with an increased prevalence of low birth weight (aPR: 1.14 [95% CI: 1.06-1.23]), preterm birth (aPR: 1.21 [95% CI: 1.13-1.30]) and cesarean delivery (aPR: 1.20 [95% CI: 1.15-1.25]), but not of small for gestational age offspring (aPR: 0.94 [95% CI: 0.88-0.99]) and birth defects (aPR: 1.01 [95% CI: 0.93-1.09]). Offspring prenatally exposed to maternal migraine had elevated risks of several outcomes in the neonatal and postnatal period, including intensive care unit admission (aRR: 1.22 [95% CI: 1.03-1.45]), hospitalization (aRR: 1.12 [95% CI: 1.06-1.18]), dispensed prescriptions (aRR: 1.34 [95% CI: 1.24-1.45]), respiratory distress syndrome (aRR: 1.20 [95% CI: 1.02-1.42]), and febrile seizures (aRR: 1.27 [95% CI: 1.03-1.57), but not of death (aRR: 0.67 [95% CI: 0.43-1.04]) and cerebral palsy (aRR: 1.00 [95% CI: 0.51-1.94]). CONCLUSIONS: Women with migraine and their offspring have greater risks of several adverse pregnancy outcomes than women without migraine.

Hip Fracture, Comorbidity, and the Risk of Myocardial Infarction and Stroke: A Danish Nationwide Cohort Study, 1995-2015.

We evaluated risks of MI and stroke in elderly patients with hip fracture compared with the general population. We also examined the interaction between hip fracture and comorbidity with respect to risks of MI or stroke, defined as excess of risk explained by combining risks of hip fracture and comorbidity. We conducted a population-based cohort study using Danish health registries, in 1995 to 2015 including 110,563 hip fracture patients and 552,774 members of the comparison cohort from the general population. Thirty-day cumulative incidences of MI were 1.15% among patients with hip fracture and 0.09% in the general population (adjusted hazard ratio [aHR] = 12.97; 95% confidence interval [CI], 11.56 to 14.55). Thirty-day cumulative incidences of stroke were 2.16% for hip fracture patients and 0.21% in the general population (aHR = 9.42; 95% CI, 8.71 to 10.19). During the 31 to 365 days following hip fracture, the aHR for MI was 1.05 (95% CI, 0.97 to 1.14) and remained at this level during the remainder of follow-up (maximum of 20 years). The aHR for stroke was 1.29 (95% CI, 1.22 to 1.35) during the 31 to 365 days following hip fracture, remained elevated for up to 10 years, and then decreased to the general population level. The aHRs for MI and stroke were increased for both men and women, and in all age and comorbidity groups. During the first 30 days, up to 76% of MI and stroke risk was attributable to interaction between hip fracture and comorbidity. Patients with hip fracture are at increased risk of both MI and stroke up to 1 year following the fracture. Risk of stroke, but not of MI, was elevated during up to 10 years postfracture. Although the absolute risks were low, our finding underscores the importance of targeting multimorbidity, including prevention and adequate treatment, to improve the prognosis of hip fracture patients. © 2017 American Society for Bone and Mineral Research.

Thirty-five-year Trends in First-time Hospitalization for Hip Fracture, 1-year Mortality, and the Prognostic Impact of Comorbidity: A Danish Nationwide Cohort Study, 1980-2014.

BACKGROUND: We examined trends in hip fracture incidence in Denmark from 1980 to 2014, trends in subsequent 1-year mortality, and the prognostic impact of sex, age, and comorbidity. METHODS: This nationwide cohort study prospectively collected data from population-based Danish registries. We included 262,437 patients with incident hip fracture and assessed comorbidity using the Charlson Comorbidity Index (CCI). RESULTS: Despite slight increases in incidence rates (IRs) of hip fracture up to the mid-1990s, the annual IR decreased by 29% from 1980 to 2014 in women but remained stable in men. Decrease affected all age groups. IR decreased in patients without comorbidity but increased with increasing comorbidity (13% in patients with moderate and 510% in patients with very severe comorbidity). Adjusted mortality rate ratios (MRRs) following hip fracture in 2010-2014 compared with 1980-1984 were 0.68 (95% confidence interval [CI] = 0.65, 0.71) within 30 days and 0.63 (95% CI = 0.61, 0.66) within 31-365 days. The mortality decreased up to 40% irrespective of comorbidity. Compared with patients with no comorbidity, those with very severe comorbidity had adjusted MRRs of 2.48 (95% CI = 2.39, 2.56) and 2.81 (95% CI = 2.74, 2.88) within 30 days and 31-365 days post-hip fracture, respectively. CONCLUSIONS: Although the incidence rate of hip fracture increased substantially with increasing comorbidity, the following 1-year mortality decreased by 40% from 1980 through 2014 irrespective of sex, age, and comorbidity level, suggesting improvement in both treatment and rehabilitation of patients with hip fracture. Comorbidity burden was, however, a strong prognostic factor for 1-year mortality after hip fracture.