Functional compared to anatomical imaging in the initial evaluation of patients with suspected coronary artery disease: An international, multi-center, randomized controlled trial (IAEA-SPECT/CTA study).

OBJECTIVE: To test the hypothesis that, in the initial evaluation of patients with suspected coronary artery disease (CAD), stress myocardial perfusion imaging (MPI) would result in less downstream testing than coronary computed tomographic angiography (CCTA). METHODS: In this international, randomized trial, mildly symptomatic patients with an intermediate likelihood of having CAD, and asymptomatic patients at intermediate risk of cardiac events, underwent either initial stress-rest MPI or CCTA. The primary outcome was downstream noninvasive or invasive testing at 6 months. Secondary outcomes included cumulative effective radiation dose (ERD) and costs at 12 months. RESULTS: We recruited 303 patients (151 MPI and 152 CTA) from 6 centers in 6 countries. The initial MPI was abnormal in 29% (41/143) and CCTA in 56% (79/141) of patients. Fewer patients undergoing initial stress-rest MPI had further downstream testing at 6 months (adjusted OR 0.51, 95% CI 0.28-0.91, P = 0.023). There was a small increase in the median cumulative ERD with MPI (9.6 vs. 8.8 mSv, P = 0.04), but no difference in costs between the two strategies at 12 months. CONCLUSION: In the management of patients with suspected CAD, a strategy of initial stress MPI is substantially less likely to require further downstream testing than initial testing with CCTA. TRIAL REGISTRATION: clinicaltrials.gov identification number NCT01368770.

The effect of various menopausal hormone therapies on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins in healthy postmenopausal women.

OBJECTIVE: Androgenic progestins such as norethisterone acetate (NETA) may influence the effect of estradiol (E(2)) therapy. We compared the influence of oral E(2), with and without NETA, and transdermal E(2) on markers of coagulation, fibrinolysis, and inflammation and on lipids and lipoproteins in healthy postmenopausal women. DESIGN: A total of 112 healthy postmenopausal women were randomized to receive treatment with either oral E(2), with or without NETA, transdermal E(2), or placebo. At baseline and after 28 weeks, levels of serum lipids and lipoproteins and markers of coagulation, fibrinolysis, and inflammation were determined. RESULTS: Of the fibrinolytic parameters, oral E(2) (P < 0.05) and E(2) with NETA (P < 0.01) shortened euglobulin clot lysis time. Oral E(2) decreased plasminogen activator inhibitor-1 activity (P < 0.05). Oral E(2) with NETA reduced plasminogen activator inhibitor-1 antigen levels (P < 0.01) and increased D-dimer antigen levels (P < 0.001). All three modes of menopausal hormone therapy reduced tissue type plasminogen activator antigen. Of the coagulation parameters, both routes of E(2) therapy decreased fibrinogen levels (P = 0.002 for oral and P = 0.007 for transdermal E(2)), whereas E(2) with NETA showed no effect. The decrease of fibrinogen was larger after oral E(2) (P = 0.02). Oral E(2) with NETA reduced antithrombin III (P < 0.001) and protein C (P < 0.001) activity. Oral E(2) (P = 0.04) and E(2) with NETA (P < 0.01) increased C-reactive protein (CRP). Transdermal E(2) showed no influence on CRP. The addition of NETA influenced the change in CRP, as the increase in CRP was more pronounced after E(2) without NETA (P = 0.005). The levels of serum amyloid A, interleukin-6, and tumor necrosis factor-alpha did not change significantly after any of the modes of hormone therapy. Of the lipids and lipoproteins, oral E2 decreased low-density lipoprotein cholesterol (P < 0.01), lipoprotein (a) (P < 0.05), and increased high-density lipoprotein cholesterol (P < 0.05). Transdermal E(2) decreased triglycerides (P < 0.02) and increased high-density lipoprotein cholesterol (P < 0.03). Oral E(2) with NETA decreased total cholesterol (P < 0.01) and high-density lipoprotein cholesterol (P < 0.005). CONCLUSIONS: Oral E(2), with or without NETA, produced no net activation of coagulation but improved fibrinolysis. Both modes of oral menopausal hormone therapy have a greater impact on markers of inflammation, coagulation, fibrinolysis, lipids, and lipoproteins than transdermal E(2). NETA attenuates some E(2) effects. Further studies are needed to elucidate the impact of these effects on clinical endpoints.