Changing predictors of statin initiation in US women over two decades

Purpose: To describe changing roles of predictors of statin initiation before and after incident coronary heart disease, and before and after publication of National Cholesterol Education Program Adult Treatment Panel-III (ATP-III) guidelines in a cohort of US women. Methods: We identified 34 382 women enrolled into the Women's Health Study from 1993 to 1995 and followed up until 2012. Proportions of previous nonusers initiating statins were described over time. We used multivariable linear regression models to estimate adjusted initiation proportion differences (IPDs) for initiation overall, separately before and after incident coronary heart disease, and separately for ATP-II and ATP-III time periods. Results: Key predictors of initiation overall were self-reported total cholesterol, and previous incident coronary heart disease, cerebrovascular disease, and diabetes. Adjusted IPDs (percentage) for total cholesterol > 240 vs <200 mg/dL were 7.5 (95% confidence interval [CI], 7.0-8.0) and 9.3 (95% CI, 8.7-9.9) during ATP-II and ATP-III time periods, respectively. Adjusted IPDs in women with diabetes were 7.0 (95% CI, 6.3-7.8) and 11.9 (95% CI, 6.7-17.0) for primary and secondary prevention, respectively, and 3.1 (95% CI, 2.1-4.0) and 9.2 (95% CI 8.2-10.2) for before and after ATP-III, respectively. Conclusions: Secular trends reflected evolution toward risk factor-based treatment indications for statin initiation with increased initiation among diabetics and women with normal and borderline cholesterol. The role of serum cholesterol changed over time, though the character was scale (multiplicative vs additive) dependent. In pharmacoepidemiologic studies of statins, strength of confounding by important variables sometimes unmeasured in claims data, such as cholesterol level, may be calendar time dependent

Incidence of venous thromboembolism following initiation of non-steroidal anti-inflammatory drugs in U.S. women

Objective: To evaluate the risk of venous thromboembolism (VTE, i.e. deep vein thrombosis or pulmonary embolism, or both) following new use of NSAIDs in a long-term cohort of U.S. women. Methods: We investigated initiation of coxibs and traditional NSAIDs (excluding aspirin) and incident VTE in 39 876 women enrolled in the Women's Health Study from 1993-95 and followed with yearly questionnaires until 2012. We defined initiation as the first reported use of NSAIDs for ≥4 days per month. Incident VTE was confirmed by an end point committee. We estimated hazard ratios (HRs) and risk differences (RDs, expressed as percentages) comparing NSAID initiation with non-initiation and acetaminophen initiation (active comparator) via standardization using a propensity score that incorporated age, BMI, calendar time, and relevant medical, behavioural, and socioeconomic variables updated over time. Results: The HR (95% CI) for risk of VTE in the as treated analyses comparing initiation with non-initiation, was 1.5 (1.2, 1.8) for any NSAID, 1.3 (1.1, 1.7) for traditional NSAIDs, and 2.0 (1.3, 3.1) for coxibs, with 2-year RDs 0.11, 0.08 and 0.32, respectively. When comparing the risk of VTE after initiation of any NSAID with that after acetaminophen initiation, the HRs were 0.9 (0.6, 1.5), 0.9 (0.5, 1.5) and 1.4 (0.6, 3.4), with 2-year RDs 0.03, -0.01, and 0.13, respectively. Conclusion: New use of NSAIDs was associated with increased VTE risk compared with non-use, but the association was null or diminished when compared with acetaminophen initiation. Elevated VTE risks associated with NSAID use in observational studies may in part reflect different baseline risks among individuals who need analgesics and may overstate the risk patients incur compared with pharmacologic alternatives