Optimal medical therapy with or without percutaneous coronary intervention in women with stable coronary disease: A pre-specified subset analysis of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial.

OBJECTIVES: To determine whether sex-based differences exist in clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in patients with stable coronary artery disease. BACKGROUND: A prior pre-specified unadjusted analysis from COURAGE showed that women randomized to PCI had a lower rate of death or myocardial infarction during a median 4.6-year follow-up with a trend for interaction with respect to sex. METHODS: We analyzed outcomes in 338 women (15%) and 1949 men (85%) randomized to PCI plus OMT versus OMT alone after adjustment for relevant baseline characteristics. RESULTS: There was no difference in treatment effect by sex for the primary end point (death or myocardial infarction; HR, 0.89; 95% CI, 0.77-1.03 for women and HR, 1.02, 95% CI 0.96-1.10 for men; P for interaction = .07). Although the event rate was low, a trend for interaction by sex was nonetheless noted for hospitalization for heart failure, with only women, but not men, assigned to PCI experiencing significantly fewer events as compared to their counterparts receiving OMT alone (HR, 0.59; 95% CI, 0.40-0.84, P < .001 for women and HR, 0.86; 95% CI, 0.74-1.01, P = .47 for men; P for interaction = .02). Both sexes randomized to PCI experienced significantly reduced need for subsequent revascularization (HR, 0.72; 95% CI, 0.62-0.83, P < .001 for women; HR, 0.84; 95% CI, 0.79-0.89, P < .001 for men; P for interaction = .02) with evidence of a sex-based differential treatment effect. CONCLUSION: In this adjusted analysis of the COURAGE trial, there were no significant differences in treatment effect on major outcomes between men and women. However, women assigned to PCI demonstrated a greater benefit as compared to men, with a reduction in heart failure hospitalization and need for future revascularization. These exploratory observations require further prospective study.

Baseline stress myocardial perfusion imaging results and outcomes in patients with stable ischemic heart disease randomized to optimal medical therapy with or without percutaneous coronary intervention.

BACKGROUND: The COURAGE trial reported similar clinical outcomes for patients with stable ischemic heart disease (SIHD) receiving optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). The current post hoc substudy analysis examined the relationship between baseline stress myocardial ischemia and clinical outcomes based on randomized treatment assignment. METHODS: A total of 1,381 randomized patients (OMT n = 699, PCI + OMT n = 682) underwent baseline stress myocardial perfusion single-photon emission computed tomographic imaging. Site investigators interpreted the extent of ischemia by the number of ischemic segments using a 6-segment myocardial model. Patients were divided into those with no to mild (<3 ischemic segments) and moderate to severe ischemia (≥ 3 ischemic segments). Cox proportional hazards models were calculated to assess time to the primary end point of death or myocardial infarction. RESULTS: At baseline, moderate to severe ischemia occurred in more than one-quarter of patients (n = 468), and the incidence was comparable in both treatment groups (P = .36). The primary end point, death or myocardial infarction, was similar in the OMT and PCI + OMT treatment groups for no to mild (18% and 19%, P = .92) and moderate to severe ischemia (19% and 22%, P = .53, interaction P value = .65). There was no gradient increase in events for the overall cohort with the extent of ischemia. CONCLUSIONS: From the COURAGE trial post hoc substudy, the extent of site-defined ischemia did not predict adverse events and did not alter treatment effectiveness. Currently, evidence supports equipoise as to whether the extent and severity of ischemia impact on therapeutic effectiveness.

Effectiveness of percutaneous coronary intervention in patients with silent myocardial ischemia (post hoc analysis of the COURAGE trial).

Previous studies have suggested that percutaneous coronary intervention (PCI) decreases long-term mortality in patients with silent myocardial ischemia (SMI), but whether PCI specifically decreases mortality when added to intensive medical therapy is unknown. We performed a post hoc analysis of clinical outcomes in patients in the COURAGE trial based on the presence or absence of anginal symptoms at baseline. Asymptomatic patients were classified as having SMI by electrocardiographic ischemia at rest or reversible stress perfusion imaging (exercise-induced or pharmacologic). Study end points included the composite primary end point (death or myocardial infarction [MI]); individual end points of death, MI, and hospitalization for acute coronary syndrome; and need for revascularization. Of 2,280 patients 12% (n = 283) had SMI and 88% were symptomatic (n = 1,997). There were no between-group differences in age, gender, cardiac risk factors, previous MI or revascularization, extent of angiographic disease, or ischemia by electrocardiogram or imaging. Compared to symptomatic patients, those with SMI had fewer subsequent revascularizations (16% vs 27%, p <0.001) regardless of treatment assignment and fewer hospitalizations for acute coronary syndrome (7% vs 12%, p <0.04). No significant differences in outcomes were observed between the 2 treatment groups, although there was a trend toward fewer deaths in the PCI group (n = 7, 5%) compared to the optimal medical therapy (OMT) group (n = 16, 11%, p = 0.12). In conclusion, addition of PCI to OMT did not decrease nonfatal cardiac events in patients with SMI but showed a trend toward fewer deaths. Although underpowered, given similar outcomes in other small studies, these findings suggest the need for an adequately powered trial of revascularization versus OMT in SMI patients.

Angiographic disease progression and residual risk of cardiovascular events while on optimal medical therapy: observations from the COURAGE Trial.

BACKGROUND: The extent to which recurrent events in patients with stable coronary artery disease is attributable to progression of an index lesion originally ≥50% diameter stenosis (DS) but not revascularized or originally <50% DS is unknown during optimal medical therapy (OMT). METHODS AND RESULTS: In the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial, 205 patients assigned to OMT plus percutaneous coronary intervention (PCI) and 284 patients assigned to OMT only had symptom-driven angiograms suitable for analysis. Percentages of patients in the OMT+PCI and OMT-only cohorts with index lesions originally <50% DS were 30% and 32%, respectively; 20% and 68% had index lesions originally ≥50% DS. In both groups, index lesions originally <50% or ≥50% DS represented <4% and <25% of all such lesions, respectively. The only angiographic predictor of myocardial infarction or acute coronary syndrome was the number of lesions originally ≥50% DS that had not been revascularized (odds ratio, 1.15; confidence limits, 1.01-1.31; P<0.04). CONCLUSIONS: Lesions originally <50% DS were index lesions in one third of patients referred for symptom-driven repeat angiography, but represented <4% of all such lesions. Nonrevascularized lesions originally ≥50% DS were more often index lesions in OMT-only patients, but still represented a minority (<25%) of all such lesions. These findings underscore the need for improved therapies to arrest plaque progression and reliable strategies for selecting stenoses warranting PCI.

Impact of metabolic syndrome and diabetes on prognosis and outcomes with early percutaneous coronary intervention in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial.

OBJECTIVES: Our purpose was to clarify the clinical utility of identifying metabolic syndrome (MetS) in patients with coronary artery disease (CAD). BACKGROUND: It is uncertain whether MetS influences prognosis in patients with CAD and whether the risk associated with MetS exceeds the risk associated with the sum of its individual components. METHODS: In a post hoc analysis, we compared the incidence of death or myocardial infarction (MI) in stable CAD patients in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial according to the presence (+) or absence (-) of MetS and diabetes: Group A, -MetS/-diabetes; Group B, +MetS/-diabetes; Group C, -MetS/+diabetes; and Group D, +MetS/+diabetes. We explored which MetS components best predicted adverse outcomes and whether MetS had independent prognostic significance beyond its individual components. RESULTS: Of 2,248 patients, 61% had MetS and 34% diabetes. Risk for death or MI increased from Group A (14%) to Group D (25%, p < 0.001). Hypertension (hazard ratio [HR]: 1.30; 95% confidence interval [CI]: 0.98 to 1.71; p = 0.07), low high-density lipoprotein cholesterol (HR: 1.26; 95% CI: 1.03 to 1.55; p = 0.03), and elevated glucose (HR: 1.17; 95% CI: 0.96 to 1.47; p = 0.11) most strongly predicted death or MI. MetS was associated with an increased risk of death or MI (unadjusted HR: 1.41; 95% CI: 1.15 to 1.73; p = 0.001). However, after adjusting for its individual components, MetS was no longer significantly associated with outcome (HR: 1.15; 95% CI: 0.79 to 1.68; p = 0.46). Allocation to initial percutaneous coronary intervention did not affect the incidence of death or MI within any group. CONCLUSIONS: Among stable CAD patients in the COURAGE trial, the presence of MetS identified increased risk for death or MI, but MetS did not have independent prognostic significance after adjusting for its constituent components. The addition of early percutaneous coronary intervention to optimal medical therapy did not significantly reduce the risk of death or MI regardless of MetS or diabetes status. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

The cost-effectiveness of percutaneous coronary intervention as a function of angina severity in patients with stable angina.

BACKGROUND: The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial compared percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) to OMT alone in reducing the risk of cardiovascular events in 2287 patients with stable coronary disease. We examined the cost-effectiveness of PCI as a function of angina severity at the time of randomization. METHODS AND RESULTS: Angina severity was assessed with the Seattle Angina Questionnaire (SAQ). Patients were grouped into tertiles based on the distribution of baseline scores such that higher tertiles represented better health status. Clinically significant improvement from baseline within individual patients was defined as score increases of >8 for physical limitation, >20 for angina frequency, and >16 for quality-of-life domains. The incremental cost-effectiveness ratio for PCI was calculated as the difference in costs divided by the difference in proportion of patients with clinically significant improvement. Improvement in angina severity was significantly greater for PCI patients in the lowest and middle tertiles. The number of patients needed to treat was much larger for the highest tertile. The added in-trial cost of PCI ranged from $7300 to $13 000. Incremental cost-effectiveness ratios ranged from $80 000 to $330 000 for the lowest and middle tertiles and from $520 000 to >$3 million for the highest tertile for 1 additional patient to achieve significant clinical improvement in health status. CONCLUSIONS: The incremental cost of PCI to provide meaningful clinical benefit above that achieved by OMT alone was lower for patients with severe angina than for those with mild or no angina. However, it is uncertain that at any level of angina severity that PCI as an initial strategy would achieve a socially acceptable cost threshold. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00007657.

Is Optimal Medical Therapy as Used in the COURAGE Trial Feasible for Widespread Use?

OPINION STATEMENT: Medical therapy is the foundation upon which all treatment for patients with stable coronary artery disease (CAD) is based, regardless of whether revascularization is performed. Although professional societies recommend comprehensive lifestyle and pharmacologic interventions with specific risk factor targets, in practice this does not usually occur. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial tested multiple simultaneous lifestyle and pharmacologic interventions (referred to as "optimal medical therapy" [OMT]) with or without percutaneous coronary intervention (PCI) in patients with stable CAD. Nurse case managers were trained to counsel patients according to protocols designed to achieve predefined lifestyle and risk factor goals. Medications were provided at no cost to patients. Adherence to lifestyle and medication prescription was very high and resulted in significant improvement in risk factor targets. COURAGE found no benefit from the addition of PCI to OMT in the primary outcome of death or myocardial infarction. OMT as delivered in COURAGE has been praised but it has also been criticized as not achievable in "real world" clinical practice. The authors, all COURAGE investigators, believe that the delivery of OMT in COURAGE represents a viable model for secondary prevention that can be translated to real practice, but acknowledge that it is difficult to do so in our fee-for-service health care system. New models of team-based healthcare to achieve evidence-based treatment targets and improved clinical outcomes are needed. Successful translation of COURAGE OMT to everyday practice will require a health care system that rewards quality of care.

Alternative strategies for the management of chronic stable angina.

The classification of patients with angina pectoris into various subgroups, which clearly differ in risk based on the patient's characteristics, is difficult. Changes in pain threshold occur frequently. The variation in intensity of the "chest discomfort" makes the history and physical of limited value in making the diagnosis. It may be necessary to use noninvasive testing to demonstrate myocardial ischemia and/or coronary angiography to define stenotic coronary artery stenosis. Within the past 30 years, there have been major advances in the successful medical and invasive treatment of angina pectoris. There are now several forms of effective therapy, which are discussed in detail in this monograph.

Do major cardiovascular outcomes in patients with stable ischemic heart disease in the clinical outcomes utilizing revascularization and aggressive drug evaluation trial differ by healthcare system?

BACKGROUND: The Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial enrolled patients from 3 distinct healthcare systems (HCSs) in North America. The primary aim of this study was to determine whether there is a treatment difference in cardiovascular outcomes by HCS. METHODS AND RESULTS: The study population included 968 patients from the US Department of Veterans Affairs (VA), 386 from the US non-VA, and 931 from Canada with different comorbidities and prognoses. The primary outcome was all-cause mortality or nonfatal myocardial infarction (MI) during the median 4.6-year follow-up. Baseline demographics were similar between percutaneous coronary intervention and optimal medical therapy treatment groups within each HCS. After follow-up, the primary end point of total mortality and nonfatal MI was not statistically significant between percutaneous coronary intervention and optimal medical therapy, regardless of HCS: VA, 22.3% versus 21.9% (hazard ratio, 1.05; 95% CI, 0.80-1.38; P=0.95); US non-VA, 15.8% versus 21.8% (hazard ratio, 0.70; 95% CI, 0.43-1.12; P=0.24); Canadian HCS, 17.3% versus 13.5% (hazard ratio, 1.30; 95% CI, 0.93-1.83; P=0.17). The interaction between HCSs and treatment was not statistically significant. Long-term mortality was significantly higher in the VA system as a result of significantly greater comorbidity and worse left ventricular function. CONCLUSIONS: In the COURAGE trial, addition of percutaneous coronary intervention to optimal medical therapy did not improve 5-year survival or reduce MI or other major adverse cardiovascular events regardless of whether patients were Canadian or American or US veterans or non-veterans. Outcome differences were largely explained by differences in baseline characteristics known to affect long-term prognosis.

Intensive multifactorial intervention for stable coronary artery disease: optimal medical therapy in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial.

OBJECTIVES: This paper describes the medical therapy used in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) trial and its effect on risk factors. BACKGROUND: Most cardiovascular clinical trials test a single intervention. The COURAGE trial tested multiple lifestyle and pharmacologic interventions (optimal medical therapy) with or without percutaneous coronary intervention in patients with stable coronary disease. METHODS: All patients, regardless of treatment assignment, received equivalent lifestyle and pharmacologic interventions for secondary prevention. Most medications were provided at no cost. Therapy was administered by nurse case managers according to protocols designed to achieve predefined lifestyle and risk factor goals. RESULTS: The patients (n = 2,287) were followed for 4.6 years. There were no significant differences between treatment groups in proportion of patients achieving therapeutic goals. The proportion of smokers decreased from 23% to 19% (p = 0.025), those who reported <7% of calories from saturated fat increased from 46% to 80% (p < 0.001), and those who walked >or=150 min/week increased from 58% to 66% (p < 0.001). Body mass index increased from 28.8 +/- 0.13 kg/m(2) to 29.3 +/- 0.23 kg/m(2) (p < 0.001). Appropriate medication use increased from pre-randomization to 5 years as follows: antiplatelets 87% to 96%; beta-blockers 69% to 85%; renin-angiotensin-aldosterone system inhibitors 46% to 72%; and statins 64% to 93%. Systolic blood pressure decreased from a median of 131 +/- 0.49 mm Hg to 123 +/- 0.88 mm Hg. Low-density lipoprotein cholesterol decreased from a median of 101 +/- 0.83 mg/dl to 72 +/- 0.88 mg/dl. CONCLUSIONS: Secondary prevention was applied equally and intensively to both treatment groups in the COURAGE trial by nurse case managers with treatment protocols and resulted in significant improvement in risk factors. Optimal medical therapy in the COURAGE trial provides an effective model for secondary prevention among patients with chronic coronary disease. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation; NCT00007657).

Optimal medical therapy with or without percutaneous coronary intervention for patients with stable coronary artery disease and chronic kidney disease.

Chronic kidney disease (CKD) is a risk factor for poor outcomes in patients with coronary artery disease (CAD), but it is unknown whether CKD influences the efficacy of alternative CAD treatment strategies. Thus, we compared outcomes in stable CAD patients with and without CKD randomized to percutaneous coronary intervention (PCI) and optimal medical therapy (OMT) or OMT alone in a post hoc analysis of the 2,287 patient COURAGE study. At baseline, 320 patients (14%) had CKD defined as a glomerular filtration rate of <60 mL/min/1.73 m(2), as estimated by the abbreviated 4-variable Modification of Diet in Renal Disease equation. The patients with CKD were older (68 +/- 9 vs 61 +/- 10 years; p <0.001) and more often had diabetes mellitus (42% vs 33%; p = 0.002), hypertension (81% vs 65%; p <0.03), heart failure (13% vs 3.4%; p <001), and three-vessel CAD (37% vs 29%, p = 0.01). After adjustment for these differences, CKD remained an independent predictor of death or nonfatal myocardial infarction (hazard ratio 1.48, 95% confidence interval 1.15 to 1.90). PCI had no effect on these outcomes. Furthermore, at 36 months, a similar percentage of patients with CKD treated with OMT (70%) and PCI plus OMT (76%) were angina free compared to patients without CKD. In conclusion, CKD is an important determinant of clinical outcomes in patients with stable CAD, regardless of the treatment strategy. Although PCI did not reduce the risk of death or myocardial infarction when added to OMT for patients with CKD, it also was not associated with worse outcomes in this high-risk group.

Quantitative results of baseline angiography and percutaneous coronary intervention in the COURAGE trial.

BACKGROUND: COURAGE compared outcomes in stable coronary patients randomized to optimal medical therapy plus percutaneous coronary intervention (PCI) versus optimal medical therapy alone. METHODS AND RESULTS: Angiographic data were analyzed by treatment arm, health care system (Veterans Administration, US non-Veterans Administration, Canada), and gender. Veterans Administration patients had higher prevalence of coronary artery bypass graft surgery and left ventricular ejection fraction < or =50%. Men had worse diameter stenosis of the most severe lesion, higher prevalence of prior coronary artery bypass graft surgery, lower left ventricular ejection fraction, and more 3-vessel disease that included a proximal left anterior descending lesion (P<0.0001 for all comparisons versus women). Failure to cross rate (3%) and visual angiographic success of stent procedures (97%) were similar to contemporary practice in the National Cardiovascular Data Registry. Quantitative angiographic PCI success was 93% (residual lesion <50% in-segment) and 82% (<20% in-stent), with only minor nonsignificant differences among health care systems and genders. Event rates were higher in patients with higher jeopardy scores and more severe vessel disease, but rates were similar irrespective of treatment strategy. Within the PCI plus optimal medical therapy arm, complete revascularization was associated with a trend toward lower rate of death or nonfatal myocardial infarction. Complete revascularization was similar between genders and among health care systems. CONCLUSIONS: PCI success and completeness of revascularization did not differ significantly by health care system or gender and were similar to contemporary practice. Angiographic burden of disease affected overall event rates but not response to an initial strategy of PCI plus optimal medical therapy or optimal medical therapy alone.

Impact of an initial strategy of medical therapy without percutaneous coronary intervention in high-risk patients from the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial.

We explored the safety and quality-of-life consequences of treating patients with stable coronary disease and high-risk features initially with optimal medical therapy (OMT) alone compared to OMT plus percutaneous coronary intervention. This was a post hoc analysis of Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial patients. We defined high risk as the onset of Canadian Cardiovascular Society class III angina within 2 months or stabilized acute coronary syndrome within 2 weeks of enrollment. The primary end point was death or myocardial infarction after 4.6 years. Of the 2,287 patients enrolled in the COURAGE trial, 264 (12%) were high risk and had a relative risk of 1.56 for death or myocardial infarction (p = 0.0008) compared to those with non-high-risk features. A total of 35 primary events occurred in the OMT group and 32 in the percutaneous coronary intervention plus OMT group (hazard ratio 1.11, 95% confidence interval 0.69 to 1.79; p = 0.68). No significant difference was found in the prevalence of angina between the 2 groups at 1 year. During the first year of follow-up, 30% of the OMT patients crossed over to the revascularization group. In conclusion, an initial strategy of OMT alone for high-risk patients in the COURAGE trial did not result in increased death or myocardial infarction at 4.6 years or worse angina at 1 year, but it was associated with a high rate of crossover to revascularization.

Optimal medical therapy with or without percutaneous coronary intervention in older patients with stable coronary disease: a pre-specified subset analysis of the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial.

OBJECTIVES: Our aim was to access clinical effectiveness of percutaneous coronary intervention (PCI) when added to optimal medical therapy (OMT) in older patients with stable coronary artery disease (CAD). BACKGROUND: While older patients with CAD are at increased risk for cardiac events compared with younger patients, it is unclear whether PCI may mitigate this risk more effectively than OMT alone or, alternatively, may be associated with more complications. METHODS: We conducted a pre-specified analysis of outcomes in stable CAD patients stratified by age and randomized to PCI+OMT or OMT alone in the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial. RESULTS: A total of 1,381 patients (60%) were <65 years of age (mean 56+/-6 years) and 904 patients (40%) were >or=65 years of age (mean 72+/-5 years). Achieved treatment targets for blood pressure, low-density lipoprotein cholesterol, adherence to diet and exercise, and angina-free status did not differ by age or treatment assignment. Among older patients, there was a 2- to 3-fold higher death rate, but similar rates of myocardial infarction, stroke, and major cardiac events compared with younger patients. The addition of PCI to OMT did not improve or worsen clinical outcomes in patients>or=65 years of age during a median 4.6 year follow-up. CONCLUSIONS: These data support adherence to American College of Cardiology/American Heart Association clinical practice guidelines that advocate OMT as an appropriate initial management strategy, regardless of age. (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation [COURAGE]; NCT00007657).

Impact of optimal medical therapy with or without percutaneous coronary intervention on long-term cardiovascular end points in patients with stable coronary artery disease (from the COURAGE Trial).

The main results of the Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation (COURAGE) trial revealed no significant differences in the primary end point of all-cause mortality or nonfatal myocardial infarction [MI] or major secondary end points (composites of death/MI/stroke; hospitalization for acute coronary syndromes [ACSs]) during a median 4.6-year follow-up in 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). We sought to assess the impact of PCI when added to OMT on major prespecified tertiary cardiovascular outcomes (time to first event), namely cardiac death and composites of cardiac death/MI, cardiac death/MI/hospitalization for ACS, cardiac death/MI/stroke, MI/stroke, or cardiac death/MI/ACS/stroke, during study follow-up. There were no significant differences between treatment arms for the composite of cardiac death or MI (15% in PCI + OMT group vs 14.2% in OMT group, hazard ratio 1.07, 95% confidence interval 0.86 to 1.33, p = 0.62) or in any of the major prespecified composite cardiovascular events during long-term follow-up, even after excluding periprocedural MI as an outcome of interest. Overall, cause-specific cardiovascular outcomes paralleled closely the primary and secondary composite outcomes of the trial as a whole. In conclusion, compared with an initial management strategy of OMT alone, addition of PCI did not decrease the incidence of major cardiovascular outcomes including cardiac death or the composite of cardiac death/MI/ACS/stroke in patients with stable coronary artery disease.

Mitral valve prolapse with a late-systolic regurgitant murmur may be associated with significant hemodynamic consequences.

The late-systolic murmur of mitral regurgitation (MR) in degenerative mitral valve disease is widely believed to represent regurgitation of a degree that is not associated with hemodynamic significance. However, the extent of left ventricular (LV) remodeling associated with the late-systolic murmur has not been systematically assessed. Accordingly, we studied 82 patients sent for evaluation of at least moderate isolated MR by echocardiography/Doppler examination. All patients had a physical examination and cardiac magnetic resonance imaging to measure LV volumes by summation of serial short-axis slices. Forty-five patients had a pan-systolic murmur and 37 had a late-systolic murmur on auscultation that was verified by timing of onset of regurgitant turbulence by cine magnetic resonance imaging. Systolic blood pressures (124 +/- 3 versus 124 +/- 3 mm Hg) and LV ejection fraction (61 +/- 1% versus 61 +/- 1%) did not differ significantly between pan-systolic and late-systolic murmur groups. Although LV end-diastolic volume index was greater in the pan-systolic versus late-systolic murmur (108 +/- 4 versus 95 +/- 4 mL/m2, P = 0.007), both groups were significantly greater than normals (68 +/- 2 mL/m2, P < 0.0001). However, LV end-systolic volume index (42 +/- 2 versus 38 +/- 2 mL/m2) and LV end-systolic dimension (38 +/- 1 versus 37 +/- 1 mm), critical markers of adverse LV remodeling in isolated MR, did not differ significantly between pan-systolic and late-systolic murmur groups. In conclusion, the late systolic isolated MR murmur may be associated with significant adverse LV remodeling, and should not be considered evidence of hemodynamically unimportant MR.

Mitral regurgitation.

Mitral regurgitation (MR) is increasingly prevalent and poses an important public health problem. There are several mechanisms through which MR can occur. Primary (organic) MR is due to intrinsic valvular disease, whereas secondary (functional) MR is due to disruption of an otherwise normal mitral apparatus because of abnormal ventricular geometry. Identification of the causative mechanism is important as this will dictate management strategy and may influence subsequent outcome. Careful assessment of MR severity is important with the use of quantitative measures. There is currently no effective medical treatment for chronic MR. Careful follow-up is paramount in the management of MR to accomplish timely surgical intervention. Mitral valve repair is preferable to valve replacement. In chronic primary MR, conventional timing of surgery is based upon appearance of symptoms and hemodynamic consequences of chronic volume overload. Optimal timing of surgery for asymptomatic patients with chronic severe MR remains controversial although there is an increasing trend toward earlier surgery. In recent years there have been significant advances in percutaneous valve interventions for MR. Although initial results are promising, longer term evaluation will answer questions concerning efficacy, durability, and safety of these interventions.

Optimal medical therapy is a proven option for chronic stable angina.

The authors of the meta-analysis of a percutaneous coronary intervention (PCI)-based invasive strategy for improving prognosis for the treatment of angina conclude that a pooling of data from various studies can be sufficiently powered to evaluate the impact of PCI on long-term mortality. However, most randomized coronary artery patient trials have insufficient power to detect significant differences in hard end points. Randomized trials in patients with chronic stable angina enroll few patients who are over age 65 years, have depressed ventricular function, have clinical instability, or who have undergone previous coronary artery bypass grafting (CABG) or PCI. "Medical therapy" today no longer means the absence of PCI, but rather the presence of intensive, evidence-based pharmacologic intervention. The COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation) trial randomized 2,287 patients to optimal medical therapy alone or optimal medical therapy plus PCI. Optimal medical therapy consisted of antiplatelet therapy, anti-ischemic therapy, and aggressive lipid and blood pressure control. Based on the strength of the evidence, the author of this commentary recommends more-aggressive medical therapy for patients with moderate-to-severe angina, and PCI or CABG for many patients in whom symptoms persist. Optimal medical therapy is a proven option for chronic stable angina.