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Clinical Trial
. 2015 Jul;8(4):357-67.
doi: 10.1161/CIRCOUTCOMES.114.001615. Epub 2015 Jul 7.

Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non-ST-Segment Elevation Acute Coronary Syndrome Patients: Insights From Clinical Trials Over 17 Years

Kristian Kragholm  1 , Sharif A Halim  1 , Qinghong Yang  1 , Phillip J Schulte  1 , Judith S Hochman  1 , Chiara Melloni  1 , Kenneth W Mahaffey  1 , David J Moliterno  1 , Robert A Harrington  1 , Harvey D White  1 , Paul W Armstrong  1 , E Magnus Ohman  1 , Frans Van de Werf  1 , Pierluigi Tricoci  1 , John H Alexander  1 , Robert P Giugliano  1 , L Kristin Newby  2
Affiliations
Clinical Trial

Sex-Stratified Trends in Enrollment, Patient Characteristics, Treatment, and Outcomes Among Non-ST-Segment Elevation Acute Coronary Syndrome Patients: Insights From Clinical Trials Over 17 Years

Kristian Kragholm et al. Circ Cardiovasc Qual Outcomes. 2015 Jul.

Abstract

Background: Adequate representation by sex in trials allows generalizability of results. We examined representation of women in clinical trials during a 17-year period in which inclusion criteria were broadened and federal mandates for representativeness were launched.

Methods and results: Using mixed models, we studied sex-stratified temporal trends in enrollment, clinical characteristics, treatment, and outcomes among 76 148 non-ST-segment elevation acute coronary syndrome patients using patient-level data merged from 11 phase III trials conducted from 1994 to 2010. Overall, 33.3% of patients were women, which changed minimally over time. Women were consistently 4 to 5 years older than men (median age 68 [interquartile range 61-75] versus 64 [interquartile range 56-72] years) and more frequently had diabetes mellitus, hypertension, and heart failure; men more frequently had prior myocardial infarction and revascularization. GRACE risk scores increased over time for both sexes with the inclusion of older patients with more comorbidities. Use of percutaneous coronary intervention, in-hospital and discharge angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers, β-blockers, and lipid-lowering drugs also increased among both sexes. Kaplan-Meier estimates of 6-month mortality declined from 7.0% [95% confidence interval 6.5%-7.6%] to 4.5% [95% confidence interval 4.0%-5.0%] among women and 6.3% [95% confidence interval 6.0%-6.7%] to 3.1% [95% confidence interval 2.9%-3.4%] among men during the 17-year period.

Conclusions: The relative proportion of women in non-ST-segment elevation acute coronary syndrome trials changed minimally over time. Nevertheless, in parallel with men, use of evidence-based care and outcomes improved significantly over time among women.

Keywords: coronary disease; myocardial infarction; women.

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Figures

Figure 1
Figure 1
Predicted versus observed 6-month mortality by sex over time. P-values are from sex and time interaction term with trial as random effect. Insignificant p-values indicate that changes in mortality rate over time are similar between women and men. KM=Kaplan-Meier observed rate for patients with calculated GRACE score; Pred=GRACE model-predicted 6-month mortality rate, not available from GUSTO IV-ACS, PRISM, PRISM-PLUS, and APPRAISE-2.
Figure 2
Figure 2
Sex-stratified trends in discharge use of lipid-lowering drugs. P-value is from sex and time interaction term with trial as random effect. Significant p-value indicates a significant difference in the trends for rates of use between women and men. Discharge use of lipid-lowering drugs was not available from GUSTO IV-ACS.
Figure 3
Figure 3
Sex-stratified trends in discharge use of ACE inhibitors/angiotensin II receptor blockers. P-value is from sex and time interaction term with trial as random effect. Significant p-value indicates a significant difference in the trends for rates of use between women and men. ACE=angiotensin-converting enzyme. Discharge use of ACE inhibitors/angiotensin II receptor blockers was not available from TRACER.
Figure 4
Figure 4. Sex-stratified trends in use of angiography and PCI
a) Trends by sex in catheterization. b) Trends by sex in PCI. P-values are from sex and time interaction term with trial as random effect. Significant p-values indicate a significant change in rates of use between women and men over time. PCI=percutaneous coronary intervention.
Figure 4
Figure 4. Sex-stratified trends in use of angiography and PCI
a) Trends by sex in catheterization. b) Trends by sex in PCI. P-values are from sex and time interaction term with trial as random effect. Significant p-values indicate a significant change in rates of use between women and men over time. PCI=percutaneous coronary intervention.
See this image and copyright information in PMC

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