Thomas K. Leong

Use of Medications for Secondary Prevention After Coronary Bypass Surgery Compared With Percutaneous Coronary Intervention

OBJECTIVES This study sought to compare use of evidence-based secondary preventive medications after coronary bypass surgery (CABG) and percutaneous coronary intervention (PCI). BACKGROUND Use of cardioprotective medication after coronary revascularization has been inconsistent and relatively low in older studies. METHODS We studied patients in a large integrated healthcare delivery system who underwent CABG or PCI for new onset coronary disease. We used data from health plan databases about prescriptions dispensed during the first year after initial coronary revascularization to identify patients who never filled a prescription and to calculate the medication possession ratio among patients who filled at least 1 prescription. We focused on angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), beta-blockers, and statins. RESULTS Between 2000 and 2007, 8,837 patients with new onset coronary disease underwent initial CABG, and 14,516 underwent initial PCI. Patients receiving CABG were more likely than patients receiving PCI to not fill a prescription for a statin (7.1% vs. 4.8%, p < 0.0001) or for an ACEI/ARB (29.1% vs. 22.4%, p < 0.0001), but similar proportions never filled a prescription for a beta-blocker (6.4% vs. 6.1%). Among those who filled at least 1 prescription post-revascularization, patients receiving CABG had lower medication possession ratios than patients receiving PCI for ACEI/ARBs (69.4% vs. 77.8%, p < 0.0001), beta-blockers (76.1% vs. 80.6%, p < 0.0001), and statins (82.7% vs. 84.2%, p < 0.001). CONCLUSIONS Patients who received CABG were generally less likely than patients who received PCI to fill prescriptions for secondary preventive medications and to use those medications consistently in the first year after the procedure.

Association of Spontaneous Bleeding and Myocardial Infarction With Long-Term Mortality After Percutaneous Coronary Intervention

BACKGROUND Platelet inhibition after percutaneous coronary intervention (PCI) reduces the risk of myocardial infarction (MI) but increases the risk of bleeding. MIs and bleeds during the index hospitalization for PCI are known to negatively affect long-term outcomes. The impact of spontaneous bleeding occurring after discharge on long-term mortality is unknown. OBJECTIVES This study sought to examine, in a real-world cohort, the association between spontaneous major bleeding or MI after PCI and long-term mortality. METHODS We conducted a retrospective cohort study of patients ≥30 years of age who underwent a PCI between 1996 and 2008 in an integrated healthcare delivery system. We used extended Cox regression to examine the associations of spontaneous bleeding and MI with all-cause mortality, after adjustment for time-updated demographics, comorbidities, periprocedural events, and longitudinal medication exposure. RESULTS Among 32,906 patients who had a PCI and survived the index hospitalization, 530 had bleeds and 991 had MIs between 7 and 365 days post-discharge. There were 4,048 deaths over a mean follow-up of 4.42 years. The crude annual death rate after a spontaneous bleed (9.5%) or MI (7.6%) was higher than among patients who experienced neither event (2.6%). Bleeding was associated with an increased rate of death (adjusted hazard ratio [HR]: 1.61, 95% confidence interval [CI]: 1.30 to 2.00), similar to that after an MI (HR: 1.91; 95% CI: 1.62 to 2.25). The association of bleeding with death remained significant after additional adjustment for the longitudinal use of antiplatelet agents. CONCLUSIONS Spontaneous bleeding after a PCI was independently associated with higher long-term mortality, and conveyed a risk comparable to that of an MI during follow-up. This tradeoff between efficacy and safety bolsters the argument for personalizing antiplatelet therapy after PCI on the basis of the patients long-term risk of both thrombotic and bleeding events.

Missed Opportunities in Cardiovascular Disease Prevention?: Low Rates of Hypertension Recognition for Women at Medicine and Obstetrics-Gynecology Clinics

Younger women use both internal medicine and obstetrics-gynecology (OBGYN) clinics as primary sources of health care. However, the role of OBGYN clinics in cardiovascular disease prevention is largely unexplored. The objective of this study was to examine rates of hypertension recognition in women <50 years of age who presented with elevated blood pressures in family practice and internal medicine (medicine) OBGYN clinics and to compare these rates across clinic type. The studys population consisted of 34 627 nonpregnant women ages 18 to 49 years with new-onset hypertension (defined as 2 consecutive visits with elevated blood pressures of systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg with no previous hypertension history) from 2002 to 2006. Multivariate logistic regressions predicting the clinical recognition of hypertension (a recorded diagnosis of hypertension and/or an antihypertensive prescription by any provider within 1 year of the second elevated blood pressure) assessed the association between hypertension recognition and the clinic where the second elevated blood pressure was recorded. Analysis showed that hypertension was recognized in <33% of women with new-onset hypertension. Women whose second consecutive elevated blood pressure was recorded in OBGYN clinics were less likely to be recognized as having hypertension within 12 months by any provider compared with women whose second consecutive elevated blood pressure was recorded in a medicine clinic (odds ratio: 0.51 [95% CI: 0.48 to 0.54]). This study suggests that further attention be paid to identifying and treating cardiovascular disease risk factors in women <50 years of age presenting in both medicine and OBGYN clinics and that improved coordination across care settings has the potential to improve cardiovascular disease prevention in young women.

Comparative effectiveness of clopidogrel in medically managed patients with unstable angina and non-ST-segment elevation myocardial infarction.

OBJECTIVES This study sought to examine the effectiveness of clopidogrel in real-world, medically managed patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI). BACKGROUND Although clinical trials have demonstrated the efficacy of clopidogrel to reduce cardiovascular (CV) morbidity and mortality in medically managed patients with UA or NSTEMI, the effectiveness of clopidogrel in actual clinical practice is less certain. METHODS A retrospective cohort study was conducted of Kaiser Permanente Northern California members without known coronary artery disease or prior clopidogrel use who presented with UA or NSTEMI between 2003 and 2008 and were medically managed (i.e., no percutaneous coronary intervention or coronary artery bypass grafting during the index hospitalization or within 7 days post-discharge). Over 2 years of follow-up, we measured the association between clopidogrel use and all-cause mortality, hospital stay for MI, and a composite endpoint of death or MI using propensity-matched multivariable Cox analyses. RESULTS We identified 16,365 patients with incident UA (35%) or NSTEMI (65%); 36% of these patients were prescribed clopidogrel within 7 days of discharge. In 8,562 propensity score-matched patients, clopidogrel users had lower rates of all-cause mortality (8.3% vs. 13.0%; p < 0.01; adjusted hazard ratio [HR]: 0.63; 95% confidence interval [CI]: 0.54 to 0.72) and the composite of death or MI (13.5% vs. 17.4%; p < 0.01; HR: 0.74, CI: 0.66 to 0.84), but not MI alone (6.7% vs. 7.2%; p = 0.30; HR: 0.93, CI: 0.78 to 1.11), compared with nonusers of clopidogrel. The association between clopidogrel use and the composite of death or MI was significant only among patients presenting with NSTEMI (HR: 0.67; CI: 0.59 to 0.76; pint < 0.01), not among those presenting with UA (HR: 1.25; CI: 0.94 to 1.67). CONCLUSIONS In a large, community-based cohort of patients who were medically managed after UA/NSTEMI, clopidogrel use was associated with a lower risk of death and MI, particularly among patients with NSTEMI.

Acute Kidney Injury After CABG Versus PCI: An Observational Study Using 2 Cohorts

BACKGROUND Acute kidney injury (AKI) is a known complication after coronary revascularization, but few studies have directly compared the incidence of AKI after coronary artery bypass surgery (CABG) or after percutaneous coronary intervention (PCI) in similar patients. OBJECTIVES The aim of this study was to investigate whether multivessel CABG compared with PCI as an initial revascularization strategy is associated with a higher risk for AKI. METHODS A retrospective analysis of patients undergoing first documented coronary revascularization was conducted using 2 complementary cohorts: 1) Kaiser Permanente Northern California, a diverse, integrated health care delivery system; and 2) Medicare beneficiaries, a large, nationally representative older cohort. AKI was defined in the Kaiser Permanente Northern California cohort by an increase in serum creatinine of ≥0.3 mg/dl or ≥150% above baseline and in the Medicare cohort by discharge diagnosis codes and the use of dialysis. RESULTS The incidence of AKI was 20.4% in the Kaiser Permanente Northern California cohort and 6.2% in the Medicare cohort. The incidence of AKI requiring dialysis was <1%. CABG was associated with a 2- to 3-fold significantly higher adjusted odds for developing AKI compared with PCI in both cohorts. CONCLUSIONS AKI is common after multivessel coronary revascularization and is more likely after CABG than after PCI. The risk for AKI should be considered when choosing a coronary revascularization strategy, and ways to prevent AKI after coronary revascularization are needed.

Coronary artery bypass grafting and percutaneous coronary intervention in patients with end-stage renal disease

OBJECTIVES To determine the relative risks of long-term mortality between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) among patients with end-stage renal disease (ESRD). METHODS We identified 1015 patients with ESRD who underwent coronary revascularization between 1996 and 2008 within Kaiser Permanente Northern California. We obtained clinical variables from health plan databases, state death certificates and social security administration files. Our primary and secondary outcomes, respectively, were all-cause mortality and repeat revascularization. Our primary predictor was CABG compared with PCI. We used a Cox proportional hazards model for multivariable analyses. RESULTS The mean age of CABG and PCI patients was similar (64.7 ± 10.6 and 63.4 ± 9.3, respectively, P = 0.06). The CABG group had a higher proportion of diabetics (P = 0.045), and higher nitrate use (P = 0.01). Adjusted for age, gender, race, year of index revascularization, number of vessels intervened, duration of dialysis and baseline comorbidities, patients referred for CABG during the first year had a hazard ratio (HR) of 1.16 [95% confidence interval (CI), 0.80-1.67] for mortality compared with PCI. During Years 1-5, the HR was 0.91 (95% CI, 0.63-1.33) with an overall HR of 0.73 (95% CI, 0.43-1.22). The sub-HR as calculated by the Fine-Gray competing risk model was 0.51 (95% CI, 0.31-0.85). CONCLUSIONS As there are no randomized clinical trials in this area, our observational study adds to the growing body of literature that suggests a significant decrease in repeat revascularization with CABG and at least equivalency in long-term mortality with CABG when compared with PCI in ESRD patients.

Temporal Trends in Mortality after Coronary Artery Revascularization in Patients with End-Stage Renal Disease

BACKGROUND Recent studies that have assessed the comparative effectiveness between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in patients with end-stage renal disease (ESRD) that have included analyses of temporal trends in mortality have noted mixed results. METHODS We conducted an observational longitudinal cohort study of all adults with ESRD undergoing CABG or PCI within Kaiser Permanente Northern California. The primary predictor, index period of revascularization, was categorized into 3 periods: 1996-1999 (reference), 2000-2003, and 2004-2008, with the primary outcome being 3-year all-cause mortality. A multivariable Cox regression model with the assumption of independent censoring was used to determine the adjusted relative risk of the primary predictor. RESULTS Among 1015 ESRD patients, 3-year mortality showed no significant change in the 2000-2003 period but was lower during the 2004-2008 period with an adjusted hazard ratio of 0.66 (95% confidence interval: 0.49-0.88; trend test p = 0.01). No change in 30-day mortality was noted. Further adjustment for receipt of medications at baseline and after revascularization did not materially affect risk estimates. No significant interactions were observed between the type of revascularization (CABG or PCI) and the period of the index revascularization. CONCLUSIONS Among a high-risk cohort of patients with ESRD and coronary artery disease within Kaiser Permanente Northern California who were referred for coronary revascularization by either CABG or PCI, the relative risk of mortality in the 2004-2008 period decreased by 34% compared with the 1996-1999 period, with the benefit primarily in the decrease in late mortality.

Association of Age to Mortality and Repeat Revascularization in End-Stage Renal Disease Patients: Implications for Clinicians and Future Health Policies

BACKGROUND The clinical effects of age occur over an age continuum, yet age as a primary predictor is often analyzed using arbitrary age cut-points. OBJECTIVE To assess whether transformation of a continuous variable such as age using a spline function can uncover nonlinear associations between age and cardiovascular outcomes. DESIGN Observational retrospective cohort study in 1015 Kaiser Permanente Northern California patients with end-stage renal disease after index coronary revascularization. Age, the primary predictor, was modeled by 5 different techniques: 1) dichotomized at 65 years or older; 2) at 80 years or older (as a sensitivity analysis); 3) categorized as younger than 55 years (reference), 55 to 64, 65 to 74, and 75 years or older; 4) linear (every 5 years) variable; and 5) nonlinear by transformation into a cubic spline. Age categories were changed in a sensitivity analysis. MAIN OUTCOME MEASURES Primary and secondary outcomes were all-cause mortality and repeat revascularization, respectively. RESULTS Graphical assessment demonstrated that age dichotomized at either 65 years and older or 80 years and older led to loss of information. Categorized age underestimated or overestimated risk at the extremes of age. A sensitivity analysis demonstrated that an arbitrary change in the age category led to a different conclusion. Age modeled linearly adequately represented mortality risk but was suboptimal with repeat revascularization. Only the cubic spline demonstrated the nonlinear association between age and repeat revascularization. CONCLUSION Employing the continuous variable age as a case study, we have demonstrated that the use of flexible transformations, such as spline functions, can unearth clinically meaningful associations that would not have been possible otherwise. Future research should determine whether incorporation of these methods can improve decision making at a population level.

Community-Based Trends in Acute Myocardial Infarction From 2008 to 2014.

Recent substantial reductions in acute myocardial infarction (AMI) rates have been reported in various patient populations [(1)][1]. Within the same health care delivery system, we extended an earlier analysis from 1999 to 2008 to examine whether these reductions have persisted into the most recent

Multimorbidity is strongly associated with long-term but not short-term mortality after cardiac valve replacement

BACKGROUND The presence of multimorbidity is known to be related to adverse clinical outcomes. However, its association with mortality in patients undergoing cardiac valve replacement is not known. METHODS Multimorbidity (as a continuous variable) was characterized in adults receiving cardiac valve replacement surgery between 2008 and 2012 within Kaiser Permanente Northern California based on information from health plan electronic health records. Our primary outcome was 3-year all-cause mortality after surgery. We used Cox proportional hazards regression to evaluate the independent association of each additional comorbidity with mortality. RESULTS Among 3686 eligible patients, mean age was 67.9±13.5years and median comorbidity burden was 3 (IQR: 2). The presence of most individual comorbidities except hypertension and hyperlipidemia did not occur in isolation. The unadjusted annual incidence (per 100 person-years) of death increased with higher comorbidity burden: ≤1: 4.61 (95% CI: 3.29-6.45), 2-3: 13.7 (95% CI: 11.9-15.8), 4-5: 23.6 (95% CI: 20.6-26.9), and ≥6: 43.4(95% CI: 34.6-54.4). Advancing age, diabetes mellitus, cerebrovascular accident, heart failure, lung disease, urgent status and use of aldosterone-receptor antagonists were independently associated with an increased risk of mortality. In multivariable analyses, each additional comorbidity was significantly associated with an increased risk of long-term (adjusted hazard ratio (HR) 1.30, 95% CI: 1.22-1.39) but not short-term mortality (HR 0.92, 95% CI: 0.80-1.07). CONCLUSIONS Our study demonstrated that multimorbidity in patients undergoing cardiac valve replacement is significantly associated with long-term but not short-term mortality.