Concomitant Treatment of Hypertensive Patients with Bisoprolol and Perindopril in Routine Clinical Practice: A Post Hoc Analysis of the CONFIDENCE II, PROTECT I, and PROTECT III Observational Studies.

INTRODUCTION: The combination of angiotensin-converting enzyme inhibitors and beta-blockers is recommended in a wide range of patients with hypertension, including those with stable coronary artery disease and/or elevated heart rate. This post hoc analysis of three observational studies provides effectiveness and safety data on treatment with perindopril on top of bisoprolol-based therapy, in routine clinical practice. METHODS: Data were analyzed from three open-label, prospective, multicenter, observational studies of Canadian patients with mild-to-moderate hypertension, which shared the same inclusion and exclusion criteria, treatment duration, and primary outcome. This post hoc analysis focused on the subpopulation of patients treated with perindopril on top of bisoprolol-based therapy. All patients were followed for 16 weeks and underwent baseline, week 4, and week 16 visits. Primary outcomes were mean changes in blood pressure (BP) and proportion of patients achieving BP control (< 140/90 mmHg) in the full analysis set (FAS). RESULTS: A total of 845 patients (mean age 68.3 ± 11.3 years, mean baseline BP 151.5/86.0 mmHg) were analyzed in the FAS. After 16 weeks, mean SBP/DBP decreased by - 20.4/- 9.8 mmHg with statistically significant reductions observed at all visits in all three studies allowing 78% of patients to achieve the BP treatment goal. No statistically significant changes in heart rate were observed and no serious adverse events reported. The most frequent doses of bisoprolol and perindopril were 5 + 4 mg (34.9%), followed by 5 + 8 mg (16.9%), and 2.5 + 4 mg (12.5%). CONCLUSION: The addition of perindopril on top of bisoprolol-based therapy in patients with mild-to-moderate hypertension was associated with significant reductions in BP compared with baseline and with achievement of BP targets in the majority of patients. The results suggest this strategy is safe and effective for use in routine clinical practice.

Use of antithrombotic therapy for secondary prevention in patients with stable atherosclerotic cardiovascular disease: Insights from the COordinated National Network to Engage Cardiologists in the antithrombotic Treatment of patients with CardioVascular Disease (CONNECT-CVD) study.

BACKGROUND: Although acetylsalicylic acid is the most commonly used antithrombotic agent for the secondary prevention of cardiovascular events, residual atherothrombotic risk has prompted a guideline recommendation for the addition of dual antiplatelet therapy (DAPT) or dual pathway inhibition (DPI) in high vascular risk patients. Accordingly, the CONNECT CVD quality enhancement initiative provides a contemporary "snapshot" of the clinical features and antithrombotic management of atherosclerotic cardiovascular disease (ASCVD) patients in Canada. METHODS: Canadian cardiologists (49 cardiologists from six provinces) undertook a retrospective chart audit of 10 ASCVD patients in their outpatient practice who met the Cardiovascular Outcomes for People Using Anticoagulation Strategy-like criteria from May 2018 to April 2019. RESULTS: Of the 492 (two cardiologists provided 11 patients) enroled, average age was 70 years, 25% were female, 39% had diabetes and 20% had atrial fibrillation. Prior revascularisation was common (percutaneous coronary artery intervention 61%, coronary artery bypass graft 39%), with 31% having multivessel disease. A total of 47% of patients had a Reduction of Atherothrombosis for Continued Health bleeding score of ≥11 (~2.8% risk of serious bleeding at 2 years). Single antiplatelet therapy (SAPT) alone was most commonly used (62%), while 22% were on DAPT alone. In total, 22% were on oral anticoagulation (OAC), with 16% being on non-vitamin K oral anticoagulant alone, 5% on DPI and 1% received triple therapy. CONCLUSIONS: In contemporary Canadian clinical practice of stable ASCVD patients, a large number of patients receive antithrombotic therapy other than SAPT. Further efforts are required to guide the appropriate selection of patients in whom more potent antithrombotic therapies may safely reduce residual risk.

The COVID-19 Pandemic and Coronary Angiography for ST-Elevation Myocardial Infarction, Use of Mechanical Support, and Mechanical Complications in Canada: A Canadian Association of Interventional Cardiology National Survey.

BACKGROUND: As a result of the COVID-19 pandemic first wave, reductions in ST-elevation myocardial infarction (STEMI) invasive care, ranging from 23% to 76%, have been reported from various countries. Whether this change had any impact on coronary angiography (CA) volume or on mechanical support device use for STEMI and post-STEMI mechanical complications in Canada is unknown. METHODS: We administered a Canada-wide survey to all cardiac catheterization laboratory directors, seeking the volume of CA use for STEMI performed during the period from March 1 2020 to May 31, 2020 (pandemic period), and during 2 control periods (March 1, 2019 to May 31, 2019 and March 1, 2018 to May 31, 2018). The number of left ventricular support devices used, as well as the number of ventricular septal defects and papillary muscle rupture cases diagnosed, was also recorded. We also assessed whether the number of COVID-19 cases recorded in each province was associated with STEMI-related CA volume. RESULTS: A total of 41 of 42 Canadian catheterization laboratories (98%) provided data. There was a modest but statistically significant 16% reduction (incidence rate ratio [IRR] 0.84; 95% confidence interval 0.80-0.87) in CA for STEMI during the first wave of the pandemic, compared to control periods. IRR was not associated with provincial COVID-19 caseload. We observed a 26% reduction (IRR 0.74; 95% confidence interval 0.61-0.89) in the use of intra-aortic balloon pump use for STEMI. Use of an Impella pump and mechanical complications from STEMI were exceedingly rare. CONCLUSIONS: We observed a modest 16% decrease in use of CA for STEMI during the pandemic first wave in Canada, lower than the level reported in other countries. Provincial COVID-19 caseload did not influence this reduction.

INTRODUCTION: Après la première vague de la pandémie de COVID-19, de nombreux pays ont déclaré une réduction de 23 % à 76 % des soins invasifs de l'infarctus du myocarde avec élévation du segment ST (STEMI). On ignore si ce changement a entraîné des répercussions sur le volume d'angiographies coronariennes (AC) ou sur l'utilisation des dispositifs d'assistance mécanique lors de STEMI et des complications mécaniques post-STEMI au Canada. MÉTHODES: Nous avons réalisé un sondage pancanadien auprès de tous les directeurs de laboratoire de cathétérisme cardiaque pour obtenir le volume d'utilisation des AC lors des STEMI réalisées durant la période du 1er mars 2020 au 31 mai 2020 (période de pandémie) et durant 2 périodes témoins (1er mars 2019 au 31 mai 2019 et 1er mars 2018 au 31 mai 2018). Le nombre de dispositifs d'assistance ventriculaire gauche utilisés et le nombre de cas de communications interventriculaires et de ruptures du muscle papillaire diagnostiqués ont également été enregistrés. Nous avons aussi évalué si le nombre de cas de COVID-19 enregistrés dans chaque province était associé au volume d'AC liées aux STEMI. RÉSULTATS: Au total, 41 des 42 laboratoires canadiens de cathétérisme (98 %) ont fourni des données. Lors de la comparaison de la première vague de la pandémie aux périodes témoins, nous avons noté une réduction modeste, mais significative, sur le plan statistique de 16 % (ratio du taux d'incidence [RTI] 0,84; intervalle de confiance à 95 % 0,80-0,87) des AC lors de STEMI. Le RTI n'était pas associé au nombre provincial de cas de COVID-19. Nous avons observé une réduction de 26 % (RTI 0,74; intervalle de confiance à 95 % 0,61-0,89) de l'utilisation de pompes à ballonnet intra-aortique lors de STEMI. L'utilisation d'une pompe Impella et les complications mécaniques après les STEMI étaient extrêmement rares. CONCLUSIONS: Nous avons observé une diminution modeste de 16 % de l'utilisation des AC lors de STEMI durant la première vague de la pandémie au Canada, soit une diminution plus faible que ce que les autres pays ont signalé. Le nombre provincial de cas de COVID-19 n'a pas influencé cette réduction.

Prognostic implications of prominent R wave in electrocardiographic leads V1 or V2 in patients with acute coronary syndrome.

Although the adverse prognosis of Q-waves on electrocardiogram (ECG) has been demonstrated, the prognostic significance of prominent R wave (PRW) in V1 or V2 across a broad spectrum of acute coronary syndrome (ACS) has not been specifically studied. In the Global Registry of Acute Coronary Events (GRACE) and the Canadian ACS Registry I ECG substudies, admission ECGs were analyzed in an independent core ECG laboratory. PRW was defined as R wave >40 to 50 ms in V1 or V2, R/S ≥1 in V1, or R/S ≥1.5 in V2. Among 11,895 patients with ACS, 495 (4.2%) had PRW; they were less likely to have a history of hypertension or heart failure and had lower GRACE risk scores, but a higher incidence of ST-segment depression (all p ≤0.001). Patients with PRW had similar rates of in-hospital death (2.8% vs 4.1%, respectively, p = 0.15) but lower rates of in-hospital heart failure (8.5% vs 15.2%, respectively, p = 0.02) and 6-month mortality (4.6% vs 8.4%, respectively, p = 0.004). In multivariable analyses, PRW was not a significant independent predictor of in-hospital mortality (adjusted odds ratio = 0.99, 95% confidence interval 0.55 to 1.8) or 6-month mortality (adjusted odds ratio = 0.70, 95% confidence interval 0.43 to 1.15). Among 4,418 patients who underwent coronary angiography, those with PRW had a higher prevalence of left circumflex artery disease (62.5% vs 49.5%, respectively, p = 0.01). In conclusion, across the broad spectrum of patients with ACS, PRW provides no significant additional prognostic utility beyond comprehensive risk assessment using the GRACE risk score. PRW is more frequently associated with left circumflex artery disease.

Atorvastatin 10 mg plus ezetimibe versus titration to atorvastatin 40 mg: attainment of European and Canadian guideline lipid targets in high-risk subjects ≥65 years.

BACKGROUND: Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients ≥65 years. METHODS: After stabilization on atorvastatin 10 mg, hypercholesterolemic subjects ≥65 years at high/very high risk for CHD and not at LDL-C <1.81 mmol/L (with atherosclerotic vascular disease [AVD]) or <2.59 mmol/L (without AVD) were randomized to ezetimibe 10 mg plus atorvastatin 10 mg or uptitration to atorvastatin 20 mg (6 weeks) followed by uptitration to 40 mg (additional 6 weeks). A post-hoc analysis compared between-group differences in percent attainment of individual and combined LDL-C, non-HDL-C and Apo B targets based on recommendations from 2012 European and Canadian Cardiovascular Society (CCS) guidelines for dyslipidemia treatment. RESULTS: Atorvastatin 10 mg plus ezetimibe produced significantly greater attainment of LDL-C, non-HDL-C, and Apo B individual and dual/triple targets vs. atorvastatin 20 mg for the entire cohort and very high-risk groups at 6 weeks. After 12 weeks, very high-risk subjects maintained significantly greater achievement of LDL-C <1.8 mmol/L (47% vs. 35%), non-HDL-C <2.6 mmol/L (63% vs. 53%) and Apo B <0.8 g/L (47% vs. 38%) single targets and dual/triple targets with atorvastatin 10 mg plus ezetimibe vs. atorvastatin 40 mg, while attainment of European target for high-risk subjects was generally similar for both treatments. Achievement of Canadian targets was significantly greater with combination therapy vs. atorvastatin 20 mg (6 weeks) or atorvastatin 40 mg (12 weeks). CONCLUSIONS: Atorvastatin 10 mg plus ezetimibe provided more effective treatment than uptitration to atorvastatin 20/40 mg for attainment of most European and Canadian guideline-recommended lipid targets in older at-risk patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00418834.

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years.

BACKGROUND: Coronary heart disease (CHD) risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients > 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 mg + ezetimibe 10 mg (EZ/Atorva) vs. increasing the atorvastatin dose to 40 mg. METHODS: Patients ≥ 65 years with atherosclerotic vascular disease (LDL-C ≥ 1.81 mmol/L) or at high risk for coronary heart disease (LDL-C ≥ 2.59 mmol/L) were randomized to EZ/Atorva for 12 wk vs. uptitration to atorvastatin 20 mg for 6 wk followed by atorvastatin 40 mg for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. RESULTS: EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients ≥ 75 years (n = 228), generally consistent with patients 65-74 years (n = 812). More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients ≥ 75 years at 12 wk. At 12 wk, more patients ≥ 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients ≥ 75 years, generally consistent with the findings in patients 65-74 years. CONCLUSIONS: Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and ≥ 75 years of age.

The comparative efficacy of ezetimibe added to atorvastatin 10 mg versus uptitration to atorvastatin 40 mg in subgroups of patients aged 65 to 74 years or greater than or equal to 75 years / 老年心脏病学杂志（英文版）

Background Coronary heart disease (CHD) risk increases with age; yet lipid-lowering therapies are significantly under-utilized in patients > 65 years. The objective was to evaluate the safety and efficacy of lipid-lowering therapies in older patients treated with atorvastatin 10 mg+ezetimibe 10 mg (EZ/Atorva) vs. increasing the atorvastatin dose to 40 mg. Methods Patients ≥ 65 years with atherosclerotic vascular disease (LDL-C ≥ 1.81 retool/L) or at high risk for coronary heart disease (LDL-C _> 2.59 mmol/L) were randomized to EZ/Atorva for 12 wk vs. upfitration to atorvastatin 20 mg for 6 wk followed by atorvastatin 40 mg for 6 wk. The percent change in LDL-C and other lipid parameters and percent patients achieving prespecified LDL-C levels were assessed after 12 wk. Results EZ/Atorva produced greater reductions in most lipid parameters vs. uptitration of atorvastatin in patients ≥ 75 years (n = 228), generally consistent with patients 65-74years (n = 812). More patients achieved LDL-C targets with combination therapy vs. monotherapy in both age groups at 6 wk and in patients ≥ 75 years at 12 wk. At 12 wk, more patients ≥ 75 years achieved LDL-C targets with monotherapy vs. combination therapy. EZ/Atorva produced more favorable improvements in most lipids vs. doubling or quadrupling the atorvastatin dose in patients ≥ 75 years, generally consistent with the findings in patients 65-74 years. Conclusions Our results extended previous findings demonstrating that ezetimibe added to a statin provided a generally well-tolerated therapeutic option for improving the lipid profile in patients 65 to 74 years and ≥ 75years of age.

Comparative efficacy of aliskiren monotherapy and ramipril monotherapy in patients with stage 2 systolic hypertension: subgroup analysis of a double-blind, active comparator trial.

Aliskiren is the first direct renin inhibitor approved for the treatment of hypertension. Blood pressure (BP) control in stage 2 hypertension with aliskiren monotherapy has not been reported. This was a post hoc analysis of the subgroup of patients with stage 2 systolic hypertension (baseline mean sitting systolic BP [msSBP]≥160 mmHg) who completed the 12-week monotherapy phase of a 6-month, double-blind, randomized study. A total of 175 patients were randomized to aliskiren 150 mg (n = 88) or ramipril 5 mg (n = 87) with optional up-titration to aliskiren 300 mg or ramipril 10 mg, respectively, at weeks 6 and 12. In the subgroup of patients with stage 2 systolic hypertension, aliskiren lowered msSBP and mean sitting diastolic BP (msDBP) by 22.3/12.7 mmHg from baseline to week 12; compared with a reduction of 18.1/10.2 mmHg with ramipril. The maximum BP reductions achieved with aliskiren were 60.0/34.0 mmHg (from a baseline of 172.7/107.3 mmHg). Aliskiren was noninferior (P < 0.0001) to ramipril for SBP reduction with nonsignificant superiority (P = 0.052), and superior (P = 0.043) to ramipril for DBP reduction. The proportion of patients who achieved BP control (<140/90 mmHg) after 12 weeks of monotherapy was larger with aliskiren (34/88, 38.6%) than with ramipril (22/87, 25.3%; P = 0.038). In this post hoc analysis, 12 weeks of monotherapy with aliskiren 150-300 mg provided effective mean BP reductions (22/13 mmHg) and was superior to ramipril 5-10 mg in controlling BP in patients with stage 2 systolic hypertension.

Safety and efficacy of ezetimibe added to atorvastatin versus up titration of atorvastatin to 40 mg in Patients > or = 65 years of age (from the ZETia in the ELDerly [ZETELD] study).

Few clinical studies have focused on the efficacy of lipid-lowering therapies in patients > or = 65 years of age. The percentage of change from baseline in low-density lipoprotein (LDL) cholesterol and the percentage of patients achieving prespecified LDL cholesterol levels after 12 weeks of ezetimibe 10 mg plus atorvastatin versus up titration of atorvastatin were assessed in subjects > or = 65 years old with hyperlipidemia and at high risk of coronary heart disease. After stabilization of atorvastatin 10-mg therapy, 1,053 patients, > or = 65 years old, at high risk of coronary heart disease, with and without atherosclerotic vascular disease and a LDL cholesterol level that was not <70 or <100 mg/dl, respectively, were randomized to receive ezetimibe added to atorvastatin 10 mg for 12 weeks versus up titration to atorvastatin 20 mg for 6 weeks followed by up titration to atorvastatin 40 mg for an additional 6 weeks. Ezetimibe added to atorvastatin 10 mg resulted in significantly greater changes at week 6 in LDL cholesterol (p <0.001), significantly more patients with atherosclerotic vascular disease achieving a LDL cholesterol level of <70 mg/dl (p <0.001), and significantly more patients without atherosclerotic vascular disease achieving a LDL cholesterol level of <100 mg/dl (p <0.001) at weeks 6 and 12 compared to atorvastatin 20 mg or atorvastatin 40 mg. In addition, ezetimibe plus atorvastatin 10 mg resulted in significantly greater changes at week 6 in total cholesterol, triglycerides, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B (all p <0.001), and HDL cholesterol (p = 0.021) compared with atorvastatin 20 mg and significantly greater changes at week 12 in LDL cholesterol, non-HDL cholesterol, apolipoprotein A-I (p = 0.001), total cholesterol, apolipoprotein B (p <0.030), and HDL cholesterol (p <0.001) compared with atorvastatin 40 mg. Both treatments were generally well tolerated, with comparable safety profiles. In conclusion, adding ezetimibe to atorvastatin 10 mg produced significantly greater favorable changes in most lipids at 6 and 12 weeks and significantly greater attainment of prespecified LDL cholesterol levels than doubling or quadrupling the atorvastatin dose in patients > or =65 years old at high risk for coronary heart disease.

Comparative effects of aliskiren-based and ramipril-based therapy on the renin system during long-term (6 months) treatment and withdrawal in patients with hypertension.

INTRODUCTION: This subgroup analysis assessed the effects of treatment based on the direct renin inhibitor, aliskiren, or the angiotensin-converting enzyme inhibitor, ramipril, on plasma renin activity (PRA), plasma renin concentration (PRC) and other biomarkers in a 26-week randomised, double-blind trial. Changes in PRA and PRC after stopping treatment were also assessed. METHODS: After placebo run-in, 842 patients (mean sitting diastolic blood pressure (BP) 95-109 mmHg) were randomised to aliskiren 150 mg or ramipril 5 mg. Dose titration and hydrochlorothiazide addition were allowed after Week 6 and 12, respectively, for inadequate BP control. Patients completing active treatment were re-randomised to current regimen or placebo during a 4-week posttreatment phase. RESULTS: BP reductions were independent of baseline PRA at Week 12, were greater with aliskiren- than ramipril-based therapy at Week 26 (17.9/13.3 vs. 15.2/12.0 mmHg, p<0.05) and persisted for longer after stopping aliskiren. Aliskiren-based therapy reduced geometric mean PRA (-63%, p<0.05; n=103), while ramipril-based therapy increased PRA (+143%, p<0.05; n=100) at Week 26; PRC increased in both groups (aliskiren: +224% [n=33], ramipril: +145% [n=39], both p<0.05). Four weeks after stopping aliskiren-based therapy, PRA remained 52% below pre-treatment baseline; PRA returned to baseline 2 weeks after stopping ramipril-based therapy. CONCLUSIONS: Aliskiren-based therapy produced sustained BP and PRA reductions over 26 weeks; ramipril-based therapy lowered BP and increased PRA. PRA reductions persisted 4 weeks after stopping aliskiren, suggesting an inhibitory effect beyond the elimination half-life of the drug.

Comparative efficacy and safety of aliskiren, an oral direct renin inhibitor, and ramipril in hypertension: a 6-month, randomized, double-blind trial.

OBJECTIVES: This double-blind study compared long-term efficacy, safety and tolerability of the oral direct renin inhibitor aliskiren and the angiotensin-converting enzyme inhibitor ramipril alone and combined with hydrochlorothiazide in patients with hypertension. METHODS: After a 2-4-week placebo run-in, 842 patients [mean sitting diastolic blood pressure (msDBP) 95-109 mmHg] were randomized to aliskiren 150 mg (n = 420) or ramipril 5 mg (n = 422). Dose titration (to aliskiren 300 mg/ramipril 10 mg) and subsequent hydrochlorothiazide addition (12.5 mg, titrated to 25 mg if required) were permitted at weeks 6, 12, 18 and 21 for inadequate blood pressure control. Patients completing the 26-week active-controlled treatment period were re-randomized to their existing regimen or placebo for a 4-week double-blind withdrawal phase. RESULTS: Six hundred and eighty-seven patients (81.6%) completed the active treatment period. At week 26, aliskiren-based therapy produced greater mean reductions in mean sitting systolic blood pressure (17.9 versus 15.2 mmHg, P = 0.0036) and msDBP (13.2 versus 12.0 mmHg, P = 0.025), and higher rates of systolic blood pressure control (< 140 mmHg; 72.5 versus 64.1%, P = 0.0075) compared with ramipril-based therapy. During withdrawal, blood pressure increased more rapidly after stopping ramipril than aliskiren-based therapy; median blood pressure reached 140/90 mmHg after 1 and 4 weeks, respectively. Blood pressure reductions were maintained with continued active treatment. Aliskiren therapy was well tolerated. Overall adverse event rates were similar with aliskiren (61.3%) and ramipril (60.4%); cough was more frequent with ramipril (9.5%) than aliskiren (4.1%). CONCLUSIONS: Aliskiren-based therapy was well tolerated and produced sustained blood pressure reductions in patients with hypertension over 6 months, greater than those with ramipril-based therapy.

Treatment and one-year outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes.

BACKGROUND: There are limited data on the treatment and long-term outcome of patients with renal dysfunction across the broad spectrum of acute coronary syndromes (ACS) in Canada. OBJECTIVES: To examine the treatment patterns and outcome of ACS patients with renal dysfunction. METHODS: In the prospective, multicentre, Canadian ACS Registry, 3510 patients hospitalized for ACS (including unstable angina, ST and non-ST elevation myocardial infarction) were categorized into four groups: normal renal function (creatinine clearance [CrCl] 90 mL/min or greater; n=1152), mild renal dysfunction (CrCl 60 mL/min to 89 mL/min; n=1253), moderate renal dysfunction (CrCl 30 mL/min to 59 mL/min; n=944) and severe renal dysfunction (CrCl less than 30 mL/min; n=161). Multivariable logistic regression analysis was performed to examine the independent prognostic value of renal dysfunction, and the association of various therapies with one-year survival. RESULTS: All-cause mortality at one year was 2.8%, 6.4%, 14.5% and 40.9% in patients with normal renal function, and mild, moderate and severe renal dysfunction, respectively (P for trend<0.001). After adjusting for other prognosticators, moderate (OR 1.82, 95% CI 1.08 to 3.08) and severe (OR 6.29, 95% CI 3.37 to 11.77) renal dysfunction remained independent predictors of one-year death. Patients with renal dysfunction were less likely to receive fibrinolytic therapy, to undergo coronary angiography and revascularization in hospital, and to be treated with acetylsalicylic acid, beta-blockers and lipid-lowering therapy at discharge and at one-year follow-up. The association of in-hospital revascularization, and discharge use of acetylsalicylic acid and beta-blockers with better one-year survival was similar among patients with normal and impaired renal function. CONCLUSIONS: Renal dysfunction is prevalent and independently predicts higher mortality in patients with ACS. The current underutilization of effective therapies may contribute to the poor outcome. There remains an important opportunity to improve care in this high-risk population.

Predictors and 1-year outcome of major bleeding in patients with non-ST-elevation acute coronary syndromes: insights from the Canadian Acute Coronary Syndrome Registries.

BACKGROUND: Bleeding is the major noncardiac adverse consequence of treatment in patients with non-ST-elevation (NSTE) acute coronary syndromes (ACS). The aims were to identify predictors of major bleeding in patients with NSTE ACS and to evaluate in-hospital and 1-year outcomes. METHODS: We evaluated 5842 patients with NSTE-ACS included in the multicenter Canadian ACS Registries. RESULTS: Patients with in-hospital major bleeding (n = 79, 1.4%) were older (75 vs 66 years, P < .001), with higher baseline creatinine (1.17 vs 1.02 mg/dL, P < .002), more diabetes (36% vs 25%, P = .04), hypertension (73% vs 54%, P < .002), previous stroke (20% vs 9%, P < .002), Killip class > or = II (P < .01), and ST-depression (37% vs 18%, P < .001). Antiplatelet/thrombotic therapies did not differ between patients with and without major bleeding. Crude event rates were significantly higher in patients with major bleeding: in-hospital death 19.2% vs 1.5% (P < .001), myocardial infarction (MI) 15.4% vs 3.8% (P < .001), and death or MI 26.9% vs 4.9% (P < .001). One-year event rates were also higher: death 35.9% vs 7.4% (P < .0001), MI 15.6% vs 6.2% (P = .0021), and death or MI 40.6% vs 12.6% (P < .0001). In multivariable analysis, independent predictors for major bleeding were age (OR 1.03, 95% CI 1.03-1.09), hypertension (1.72, 1.0-2.97), previous stroke (1.84, 1.0-3.37), and in-hospital catheterization (1.93, 1.06-3.53) or bypass surgery (2.18, 1.0-4.76). Major bleeding was an independent predictor of 1-year death (OR 3.92, 2.07-7.41) and death or MI (2.51, 1.41-4.48). CONCLUSIONS: In patients with NSTE-ACS, major bleeding is associated with increased short- and long-term rates of death and MI, and is predicted by simple clinical characteristics.

Statin therapy and the management of acute coronary syndromes.

The pathophysiology of acute coronary syndromes is related to erosion or rupture of vulnerable plaque leading to intracoronary thrombosis as a result of activation of the coagulation cascade and platelet aggregation. Potential benefit of hypolipidemic 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibition may be related to the pleiotropic effects such as endothelial function improvement, stabilization of the plaque in relation to reduced macrophage activity and smooth muscle cell proliferation, as well as other anti-inflammatory effects that have been demonstrated in animal models. With the publication of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, early initiation of statin therapy within 24 to 96 h has been recognized as an important addition to the therapeutic armamentarium in the management of patients with acute coronary syndromes.