Prevalence and management of hypertension in acute coronary syndrome patients varies by sex: observations from the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events postacute cOroNary sYndromes (SYMPHONY) randomized clinical trials.

BACKGROUND: Hypertension affects 1 billion individuals worldwide and is an independent risk factor for death after acute coronary syndromes (ACS). METHODS: We examined the prevalence and medical treatment of hypertension among 15,904 ACS patients randomized in the SYMPHONY and 2nd SYMPHONY trials. Analyses were performed overall and according to sex for the United States and across international practice. Multivariable models identified factors associated with use of antihypertensive medication classes and examined the association of hypertension and sex with mortality. RESULTS: In the United States, hypertension was more prevalent in women than in men, overall (63% vs 50%) and within every decile of age. Hypertensive women more often received calcium-channel blockers (35% vs 30%) and diuretics (33% vs 19%) and less often received beta-blockers (51% vs 57%). Angiotensin-converting enzyme inhibitor use was similar (35% vs 34%). Women received multiple agents more frequently than did men: 2 agents, 35% vs 30%; > or = 3 agents, 16% vs 13%. Female sex independently predicted drug-class use only for diuretics. Mortality was higher in hypertensive women than in hypertensive men; after multivariable adjustment, mortality was similar without evidence of a differential association between hypertension and mortality according to sex. Although there was international variation in the use of individual classes of agents, the overall findings by sex were similar across regions. CONCLUSION: Hypertension is more prevalent in women than in men with ACS, and its medical management varies by sex, but its association with mortality is similar. Opportunities exist to improve medical therapy and outcomes in women with hypertension.

Continuous haemodynamic monitoring during exercise in patients with pulmonary hypertension.

BACKGROUND: Right heart haemodynamic parameters can be recorded continuously with the help of an implanted haemodynamic monitor. Aim of the study was to assess the haemodynamic response with and without inhalation of iloprost during cardiopulmonary exercise testing (CPET) in patients with pulmonary hypertension. MATERIALS AND METHODS: Five female patients with documented pulmonary hypertension (mean +/- S.D. age 47 +/- 16 years, 4 arterial, 1 venous) previously implanted with a haemodynamic monitor underwent an incremental exercise test on 2 separate days. The tests were performed before and immediately after inhalation of a single dose of iloprost (17 microg). Parameters recorded by the device were right ventricular (RV)-afterload (RV systolic pressure, RVSP), RV-preload (RV diastolic pressure, RVDP), estimated pulmonary artery diastolic pressure (ePAD), heart rate (HR) and maximum positive rate of RV pressure development (RVdP/dt) (reflecting the dynamic and inotropic state of the RV). RESULTS: After inhalation of iloprost, RV systolic pressure was always reduced at rest. It was followed by an increase with higher workloads without any difference at VO(2peak). The time course of RV systolic pressure was not linear with a flattening at higher workload during the test. This behaviour was found irrespective of iloprost treatment. The remaining determinants of RV performance showed no relevant differences and a linear behaviour during the exercise test. CONCLUSIONS: Inhalation of aerosolised iloprost resulted in a reduction in right ventricular pressure at rest but not at maximal workload. The implantable haemodynamic monitor (IHM) may be useful for the evaluation of RV haemodynamics during exercise and in assessing treatment efficacy.

Association of diabetes mellitus and glycemic control strategies with clinical outcomes after acute coronary syndromes.

BACKGROUND: Diabetes is associated with an increased risk for coronary artery disease (CAD) and its complications. The relative effect of glucose-lowering strategies of "insulin provision" versus "insulin sensitization" among patients with CAD remains unclear. METHODS: To evaluate the associations of diabetes and hypoglycemic strategies with clinical outcomes after acute coronary syndromes, we analyzed data from 15,800 patients enrolled in the SYMPHONY and 2nd SYMPHONY trials. RESULTS: Compared with nondiabetic patients, patients with diabetes (n = 3101; 19.6%) were older, more often female, more often had prior CAD, hypertension, and hyperlipidemia, and less often were current smokers. The diabetic cohort had higher 90-day unadjusted risk of the composite of death/myocardial infarction (MI)/severe recurrent ischemia (SRI), death/MI, and death alone, as well as a near doubling of 1-year mortality rates. At 1 year, diabetes was associated with significantly higher adjusted risks of death/MI/SRI (OR, 1.3 [95% confidence interval, 1.1, 1.5]) and death/MI (OR, 1.2 [1.0, 1.4]). Hypoglycemic therapy including only insulin and/or sulfonylurea (insulin-providing; n = 1473) was associated with higher 90-day death/MI/SRI compared with therapy that included only biguanide and/or thiazolidinedione therapy (insulin-sensitizing; n = 100) (12.0% vs 5.0%); (adjusted OR, 2.1 [1.2, 3.7]). CONCLUSIONS: Diabetic patients with acute coronary syndromes had worse clinical outcomes. Although the findings regarding the influence of glycemic-control strategies should be interpreted with caution because of the exploratory nature of the analyses and the relatively small sample size of the insulin-sensitizing group, the improved risk-adjusted outcomes associated with insulin-sensitizing therapy underscore the need to further evaluate treatment strategies for patients with diabetes and CAD.

Efficacy and tolerability of trimetazidine in stable angina: a meta-analysis of randomized, double-blind, controlled trials.

OBJECTIVE: The objective of this meta-analysis was to evaluate the efficacy and tolerance of the metabolic agent trimetazidine (TMZ), both in monotherapy and in combination with other antianginal agents, in the treatment of stable angina pectoris. A search of literature published between 1985 and 2001 was performed on computerized databases (MEDLINE and EMBASE). METHODS: Only double-blind, randomized, controlled trials were included in this meta-analysis. Patients had to be treated for at least 2 weeks. Four parameters were selected, one clinical parameter (number of weekly angina attacks) and three ergometric parameters (time to 1 mm ST-segment depression, total work and exercise duration at peak exercise). They were evaluated at baseline and at the end of the treatment period.The quality of the trials was assessed on specific methodological criteria. Standard statistical methods, pooled odds ratio and 95% confidence intervals for subjective symptoms and pooled z and P for objective symptoms, were used. RESULTS: Twelve clinical studies meeting our criteria were analyzed. Results showed that TMZ significantly reduced the number of weekly angina attacks in coronary patients and improved time to 1 mm segment depression and total work at peak exercise, while exercise duration at peak exercise showed a trend toward improvement (P = 0.09). CONCLUSION: This meta-analysis confirms the efficacy of TMZ in the treatment of stable angina, compared with placebo or conventional antianginal agent, as well as in monotherapy or in combination with conventional antianginal agents. TMZ is well tolerated in monotherapy as well as in combination.

Early statin initiation and outcomes in patients with acute coronary syndromes.

CONTEXT: The secondary prevention benefit of therapy with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) has been clearly demonstrated; however, the role of early initiation of statins after acute coronary syndromes (ACSs) is unknown. OBJECTIVE: To evaluate the association of early statin initiation (< or = 7 days) after ACS with 90-day and 1-year outcomes. DESIGN: Observational cohort from databases of 2 randomized clinical trials, SYMPHONY and 2nd SYMPHONY. SETTING: Nine hundred thirty-one clinical centers in 37 countries. PATIENTS: A total of 12,365 ACS patients randomized from August 1997 to August 1999 who were not taking statins prior to the index ACS and who either started statin therapy early (median, 2.0 [interquartile range, 1.0-3.1] days after ACS; n = 3952) or survived more than 5 days after ACS and never received statin therapy (n = 8413). MAIN OUTCOME MEASURES: Ninety-day incidence of death; death or myocardial infarction (MI); and death, MI, or severe recurrent ischemia; as well as 1-year incidence of death. RESULTS: Ninety-day and 1-year unadjusted mortality comparison suggested early statin benefit (1.2% for early statins vs 2.1% for no statins; hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.42-0.81 for 90-day comparisons and 2.3% for early statins vs 4.4% for no statins; HR, 0.52; 95% CI, 0.40-0.68 for 1-year comparison). However, no benefit was evident for 90-day death or MI (6.5% vs 6.9%; HR, 0.95; 95% CI, 0.82-1.11) or death, MI, or severe recurrent ischemia (9.2% vs 8.9%; HR, 1.04; 95% CI, 0.92-1.18). After propensity and covariate adjustment, there were no 90-day or 1-year differences between the early-statin group and the no-statin group. The 90-day adjusted HR for death was 1.08 (95% CI, 0.75-1.56); for death or MI, 1.08 (95% CI, 0.91-1.29); and for death, MI, or severe recurrent ischemia, 1.15 (95% CI, 0.99-1.34). One-year mortality-adjusted HR was 0.99 (95% CI, 0.73-1.33). Among 2711 patients with core laboratory lipid analysis, early statin was associated with higher adjusted risk for death or death or MI at cholesterol levels below treatment guidelines but was more favorable at higher levels. CONCLUSIONS: In this study, there was no relationship between early initiation of statin therapy and improved outcomes although our subset analysis suggests that outcomes after early statin initiation may vary with cholesterol levels. Confirmation of early treatment effects of statins on outcomes awaits the results of adequately powered randomized clinical trials.

Efficacy of monotherapy compared with combined antianginal drugs in the treatment of chronic stable angina pectoris: a meta-analysis.

OBJECTIVE: To determine the relative efficacy of antianginal drugs administered as monotherapy or in combination in patients with chronic stable angina. METHODS: A meta-analysis was performed on randomized trials, published in English between 1980 and 1999, that directly compared combined treatment and monotherapy. Twenty-two articles were included, all on the comparison of -blocker monotherapies to their combination with a calcium antagonist and 10 on the comparison of calcium antagonist monotherapies to their combination with a -blocker. RESULTS: Time to 1 mm ST-segment depression, total exercise duration and time to onset of anginal pain were significantly increased with the combined therapy compared to -blocker alone (by 8, 5 and 12%, respectively). Only time to 1 mm ST-segment depression was significantly increased with the combined therapy compared to calcium antagonist alone (by 9%). For all these parameters, the adjusted differences were significant only within 6 h following drug intake and were not significant after 6 h. No analysis of safety data could be performed. CONCLUSION: As far as exercise testing is concerned, the combination of a calcium antagonist and a -blocker is statistically more effective than either monotherapy. Further studies are needed to confirm the higher efficacy after the first 6 h following drug intake.