Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. METHODS: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Management of dyslipidemia for cardiovascular disease risk reduction: synopsis of the 2014 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline.

DESCRIPTION: In December 2014, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline for the management of dyslipidemia for cardiovascular disease risk reduction in adults. This synopsis summarizes the major recommendations. METHODS: On 30 September 2013, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature, developed a simple 1-page algorithm, and rated each of 26 recommendations by using the Grading of Recommendations Assessment, Development, and Evaluation system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 5 areas: elimination of treatment targets, additional tests for risk prediction, primary and secondary prevention, and laboratory testing.

The effect of statin therapy on heart failure events: a collaborative meta-analysis of unpublished data from major randomized trials.

AIMS: The effect of statins on risk of heart failure (HF) hospitalization and HF death remains uncertain. We aimed to establish whether statins reduce major HF events. METHODS AND RESULTS: We searched Medline, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized controlled endpoint statin trials from 1994 to 2014. Collaborating trialists provided unpublished data from adverse event reports. We included primary- and secondary-prevention statin trials with >1000 participants followed for >1 year. Outcomes consisted of first non-fatal HF hospitalization, HF death and a composite of first non-fatal HF hospitalization or HF death. HF events occurring <30 days after within-trial myocardial infarction (MI) were excluded. We calculated risk ratios (RR) with fixed-effects meta-analyses. In up to 17 trials with 132 538 participants conducted over 4.3 [weighted standard deviation (SD) 1.4] years, statin therapy reduced LDL-cholesterol by 0.97 mmol/L (weighted SD 0.38 mmol/L). Statins reduced the numbers of patients experiencing non-fatal HF hospitalization (1344/66 238 vs. 1498/66 330; RR 0.90, 95% confidence interval, CI 0.84-0.97) and the composite HF outcome (1234/57 734 vs. 1344/57 836; RR 0.92, 95% CI 0.85-0.99) but not HF death (213/57 734 vs. 220/57 836; RR 0.97, 95% CI 0.80-1.17). The effect of statins on first non-fatal HF hospitalization was similar whether this was preceded by MI (RR 0.87, 95% CI 0.68-1.11) or not (RR 0.91, 95% CI 0.84-0.98). CONCLUSION: In primary- and secondary-prevention trials, statins modestly reduced the risks of non-fatal HF hospitalization and a composite of non-fatal HF hospitalization and HF death with no demonstrable difference in risk reduction between those who suffered an MI or not.

Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: a meta-analysis.

BACKGROUND: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. METHODS AND RESULTS: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38,153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97). CONCLUSIONS: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Association of azithromycin with mortality and cardiovascular events among older patients hospitalized with pneumonia.

IMPORTANCE: Although clinical practice guidelines recommend combination therapy with macrolides, including azithromycin, as first-line therapy for patients hospitalized with pneumonia, recent research suggests that azithromycin may be associated with increased cardiovascular events. OBJECTIVE: To examine the association of azithromycin use with all-cause mortality and cardiovascular events for patients hospitalized with pneumonia. DESIGN: Retrospective cohort study comparing older patients hospitalized with pneumonia from fiscal years 2002 through 2012 prescribed azithromycin therapy and patients receiving other guideline-concordant antibiotic therapy. SETTING: This study was conducted using national Department of Veterans Affairs administrative data of patients hospitalized at any Veterans Administration acute care hospital. PARTICIPANTS: Patients were included if they were aged 65 years or older, were hospitalized with pneumonia, and received antibiotic therapy concordant with national clinical practice guidelines. MAIN OUTCOMES AND MEASURES: Outcomes included 30- and 90-day all-cause mortality and 90-day cardiac arrhythmias, heart failure, myocardial infarction, and any cardiac event. Propensity score matching was used to control for the possible effects of known confounders with conditional logistic regression. RESULTS: Of 73,690 patients from 118 hospitals identified, propensity-matched groups were composed of 31,863 patients exposed to azithromycin and 31,863 matched patients who were not exposed. There were no significant differences in potential confounders between groups after matching. Ninety-day mortality was significantly lower in those who received azithromycin (exposed, 17.4%, vs unexposed, 22.3%; odds ratio [OR], 0.73; 95% CI, 0.70-0.76). However, we found significantly increased odds of myocardial infarction (5.1% vs 4.4%; OR, 1.17; 95% CI, 1.08-1.25) but not any cardiac event (43.0% vs 42.7%; OR, 1.01; 95% CI, 0.98-1.05), cardiac arrhythmias (25.8% vs 26.0%; OR, 0.99; 95% CI, 0.95-1.02), or heart failure (26.3% vs 26.2%; OR, 1.01; 95% CI, 0.97-1.04). CONCLUSIONS AND RELEVANCE: Among older patients hospitalized with pneumonia, treatment that included azithromycin compared with other antibiotics was associated with a lower risk of 90-day mortality and a smaller increased risk of myocardial infarction. These findings are consistent with a net benefit associated with azithromycin use.

Long-term cardiovascular risks and the impact of statin treatment on socioeconomic inequalities: a microsimulation model.

BACKGROUND: UK cardiovascular disease (CVD) incidence and mortality have declined in recent decades but socioeconomic inequalities persist. AIM: To present a new CVD model, and project health outcomes and the impact of guideline-recommended statin treatment across quintiles of socioeconomic deprivation in the UK. DESIGN AND SETTING: A lifetime microsimulation model was developed using 117 896 participants in 16 statin trials, 501 854 UK Biobank (UKB) participants, and quality-of-life data from national health surveys. METHOD: A CVD microsimulation model was developed using risk equations for myocardial infarction, stroke, coronary revascularisation, cancer, and vascular and non-vascular death, estimated using trial data. The authors calibrated and further developed this model in the UKB cohort, including further characteristics and a diabetes risk equation, and validated the model in UKB and Whitehall II cohorts. The model was used to predict CVD incidence, life expectancy, quality-adjusted life years (QALYs), and the impact of UK guideline-recommended statin treatment across socioeconomic deprivation quintiles. RESULTS: Age, sex, socioeconomic deprivation, smoking, hypertension, diabetes, and cardiovascular events were key CVD risk determinants. Model-predicted event rates corresponded well to observed rates across participant categories. The model projected strong gradients in remaining life expectancy, with 4-5-year (5-8 QALYs) gaps between the least and most socioeconomically deprived quintiles. Guideline-recommended statin treatment was projected to increase QALYs, with larger gains in quintiles of higher deprivation. CONCLUSION: The study demonstrated the potential of guideline-recommended statin treatment to reduce socioeconomic inequalities. This CVD model is a novel resource for individualised long-term projections of health outcomes of CVD treatments.

Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumonia-related outcomes.

BACKGROUND: Studies suggest that statins and angiotensin-converting enzyme (ACE) inhibitors might be beneficial for the treatment of infections. Our purpose was to examine the association of statin, ACE inhibitor, and angiotensin II receptor blocker (ARB) use with pneumonia-related outcomes. METHODS: We conducted a retrospective cohort study using Department of Veterans Affairs data of patients aged ≥ 65 years hospitalized with pneumonia. We performed propensity-score matching for 3 medication classes simultaneously. RESULTS: Of 50119 potentially eligible patients, we matched 11498 cases with 11498 controls. Mortality at 30 days was 13%; 34% used statins, 30% ACE inhibitors, and 4% ARBs. In adjusted models, prior statin use was associated with decreased mortality (odds ratio [OR], 0.74; 95% confidence interval [CI], .68-.82) and mechanical ventilation (OR, 0.81; 95% CI, .70-.94), and inpatient use with decreased mortality (OR, 0.68; 95% CI, .59-.78) and mechanical ventilation (OR, 0.68; 95% CI, .60-.90). Prior (OR, 0.88; 95% CI, .80-.97) and inpatient (OR, 0.58; 95% CI, .48-.69) ACE inhibitor use was associated with decreased mortality. Prior (OR, 0.73; 95% CI, .58-.92) and inpatient ARB use (OR, 0.47; 95% CI, .30-.72) was only associated with decreased mortality. Use of all 3 medications was associated with reduced length of stay. CONCLUSIONS: Statins, and to a lesser extent ACE inhibitors and ARBs, are associated with improved pneumonia-related outcomes. Prospective cohort and randomized controlled trials are needed to examine potential mechanisms of action and whether acute initiation at the time of presentation with these infections is beneficial.

Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis.

CONTEXT: The associations of low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (apoB) levels with the risk of cardiovascular events among patients treated with statin therapy have not been reliably documented. OBJECTIVE: To evaluate the relative strength of the associations of LDL-C, non-HDL-C, and apoB with cardiovascular risk among patients treated with statin therapy. DESIGN: Meta-analysis of individual patient data from randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. DATA SOURCES: Relevant trials were identified by a literature search updated through December 31, 2011. Investigators were contacted and individual patient data were requested and obtained for 62,154 patients enrolled in 8 trials published between 1994 and 2008. DATA EXTRACTION: Hazard ratios (HRs) and corresponding 95% CIs for risk of major cardiovascular events adjusted for established risk factors by 1-SD increase in LDL-C, non-HDL-C, and apoB. RESULTS: Among 38,153 patients allocated to statin therapy, 158 fatal myocardial infarctions, 1678 nonfatal myocardial infarctions, 615 fatal events from other coronary artery disease, 2806 hospitalizations for unstable angina, and 1029 fatal or nonfatal strokes occurred during follow-up. The adjusted HRs for major cardiovascular events per 1-SD increase were 1.13 (95% CI, 1.10-1.17) for LDL-C, 1.16 (95% CI, 1.12-1.19) for non-HDL-C, and 1.14 (95% CI, 1.11-1.18) for apoB. These HRs were significantly higher for non-HDL-C than LDL-C (P = .002) and apoB (P = .02). There was no significant difference between apoB and LDL-C (P = .21). CONCLUSION: Among statin-treated patients, on-treatment levels of LDL-C, non-HDL-C, and apoB were each associated with risk of future major cardiovascular events, but the strength of this association was greater for non-HDL-C than for LDL-C and apoB.

Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.

BACKGROUND: Trials of statin therapy have had conflicting findings on the risk of development of diabetes mellitus in patients given statins. We aimed to establish by a meta-analysis of published and unpublished data whether any relation exists between statin use and development of diabetes. METHODS: We searched Medline, Embase, and the Cochrane Central Register of Controlled Trials from 1994 to 2009, for randomised controlled endpoint trials of statins. We included only trials with more than 1000 patients, with identical follow-up in both groups and duration of more than 1 year. We excluded trials of patients with organ transplants or who needed haemodialysis. We used the I(2) statistic to measure heterogeneity between trials and calculated risk estimates for incident diabetes with random-effect meta-analysis. FINDINGS: We identified 13 statin trials with 91 140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1.09; 95% CI 1.02-1.17), with little heterogeneity (I(2)=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150-852) patients with statins for 4 years resulted in one extra case of diabetes. INTERPRETATION: Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change. FUNDING: None.

Pneumonia in the elderly hospitalized in the Department of Veteran Affairs Health Care System.

Pneumonia is a major cause of hospital admissions and deaths worldwide. Our aim was to examine the trends in admissions for pneumonia in the Department of Veterans Affairs (VA). We examined data for the fiscal years 2002 through 2007 on patients aged 65 years and older hospitalized with pneumonia by using VA administrative databases. The numbers of hospital admissions for pneumonia were relatively stable during this period. However, length of hospital stay and 30- and 90-day mortality decreased during this period. The proportion of patients admitted to the intensive care unit remained relatively constant, but fewer received mechanical ventilation; there was substantial increase in noninvasive ventilation. In the VA, pneumonia-related admissions are being managed more effectively even as the overall number of admissions remains stable.

Prediabetes assessment and follow-up in older veterans with schizophrenia.

OBJECTIVES: Assess glycemic monitoring and follow-up. DESIGN: Retrospective study using administrative data (October 2001-September 2005). SETTING: Veterans Health Administration. PARTICIPANTS: A nationwide sample of 39,226 outpatients aged 50 years or older with schizophrenia. Patients had no diagnosis or medications for diabetes at baseline. MEASUREMENTS: Hemoglobin A1c tests; blood glucose tests with same-day low-density lipoprotein to approximate fasting glucose. Glycemic tests were combined to indicate a) prediabetic dysglycemia (100-125 mg/dL proxy fasting glucose or 5.8%-6.4% hemoglobin A1c) and b) diabetic dysglycemia (≥126 proxy fasting glucose or ≥6.5% A1c). RESULTS: Approximately one-third of patients (32%; 12,587) had proxy fasting blood glucose or A1c tests in 2002; multiple tests were rare. The proportion tested increased to 40% by 2005. Test results suggested prediabetic dysglycemia for 5,345 tested patients (42% of those tested) and diabetic dysglycemia for 1,287 tested patients (10%) at baseline. In multivariate regression models, glycemic testing was associated with dyslipidemia, hypertension, and younger age. Dysglycemia was associated with hypertension, dyslipidemia, and older age. Follow-up treatment/diagnosis of diabetes occurred for 8% of patients (11% of those tested) and was associated with baseline dysglycemia, hypertension, and younger age. Mortality (15% during the 4-year study) was higher among untested and untreated patients. CONCLUSIONS: Dysglycemia was prevalent among older patients with schizophrenia, although monitoring and follow-up were uncommon. Follow-up treatment correlated with survival. Despite evident utility of testing, few at-risk patients with schizophrenia were adequately monitored, diagnosed, or treated for dysglycemia.

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR.

Plasma homocysteine concentration, statin therapy, and the risk of first acute coronary events.

BACKGROUND: Elevated homocysteine levels are associated with increased coronary risk, and it has been suggested that homocysteine screening may provide a method to identify high-risk patients for aggressive primary prevention. METHODS AND RESULTS: Homocysteine was measured at baseline and after 1 year among 5569 participants in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS), a randomized trial of lovastatin in the primary prevention of acute coronary events. The effects of homocysteine, LDL cholesterol, and lovastatin on risk were assessed over 5.2 years of trial follow-up. Median baseline homocysteine levels were significantly higher among study participants who subsequently had acute coronary events compared with those who did not (12.1 versus 10.9 micro;mol/L, P<0.001). The relative risks of future events from lowest (referent) to highest quartile of homocysteine were 1.0, 1.6, 1.6, and 2.2 (P<0.001). These effects were similar among those allocated to lovastatin and those allocated to placebo and were modestly attenuated after adjustment for other traditional risk factors. As predicted, the subgroup of participants with elevated LDL cholesterol and elevated homocysteine levels were at high risk and benefited greatly from statin therapy (relative risk, 0.46; 95% CI, 0.29 to 0.75; number needed to treat=26). However, in contrast to findings in this trial for C-reactive protein, homocysteine evaluation did not help to define low LDL subgroups with different responses to lovastatin therapy. CONCLUSIONS: Although homocysteine predicted future coronary events in AFCAPS/TexCAPS, we found little evidence that homocysteine evaluation provided an improved method to target statin therapy among those with low-to-normal LDL cholesterol levels.

Implications from the Air Force/Texas Coronary Atherosclerosis Prevention Study for the Adult Treatment Panel III guidelines.

The Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) first reported its results in 1998, before the 2001 publication of the National Cholesterol Education Program-Adult Treatment Panel III guidelines (NCEP-ATP III) and 2004 update. Our objective was to investigate the impact of these guidelines on the AFCAPS/TexCAPS cohort. The main outcome measures were the event rates of first acute major coronary events (AMCEs), which were reduced 39% by lovastatin (95% confidence interval [CI] 21% to 53%, p <0.001) in the 65% of the cohort eligible for drug therapy and by 34% (95% CI -9% to 60%, p = 0.108) in the remaining 35% for whom drug therapy was considered optional. The evaluation of other guideline components included a 44% (95% CI 27% to 58%, p <0.001) reduction in AMCEs in subjects with baseline high-density lipoprotein cholesterol <40 mg/dl and a 41% (95% CI 19% to 57%) reduction in AMCEs in subjects with the metabolic syndrome. In the recent update, patients who had a moderately high risk of coronary heart disease and a baseline low-density lipoprotein cholesterol level of 100 to 130 mg/dl could be considered for therapy with a medication to lower the low-density lipoprotein cholesterol level to <100 mg/dl. A total of 334 subjects (5.1%) were in this group, in whom lovastatin reduced the risk of AMCEs by 68% (95% CI 12% to 88%, p = 0.027). However, 21% of the AMCEs were missed by the guidelines. Metabolic syndrome was noted in 48% of these subjects and may help define those in whom treatment with a medication is now considered optional. In conclusion, the ability of the ATP III guidelines and its update has markedly improved our ability to define coronary heart disease risk; however, other components of the guidelines, such as non-high-density lipoprotein cholesterol and the optional low-density lipoprotein cholesterol target goal of <100 mg/dl, still require additional evaluation.

Statins and Finasteride Use Differentially Modify the Impact of Metformin on Prostate Cancer Incidence in Men with Type 2 Diabetes.

BACKGROUND: Metformin has shown promise for cancer prevention. Prior studies suggested that metformin might interact potential prostate cancer (PCa) prevention agents: finasteride and statins. This study assessed if concurrent use of statins or finasteride modified the long-term impact of metformin on PCa risk in men with type 2 diabetes (T2DM). MATERIALS AND METHODS: The study cohort consisted of 71,999 men with T2DM seen in the Veteran Administration Health Care System, without prior cancer or liver diseases, nor prescription of thiazolidinediones or insulin between FY2003-FY2013. Cox proportional hazard analyses (adjusting for covariates and propensity scores of metformin use) were conducted to compare the hazard ratio (HR) of PCa associated with metformin use between statins or finasteride users and none users. RESULTS: Mean follow-up was 6.4±2.8 years; 5.2% (N= 3,756) of the cohort subsequently received a PCa diagnosis. Both statins and finasteride significantly modified the impact of metformin on PCa incidence (p-value<0.001): HR's of PCa associated with metformin use were 0.89 (p-value=0.02) among non-statin/non-finasteride users, 0.73 (p-value<0.001) among statin users, and 1.42 (p-value<0.001) among finasteride users. CONCLUSION: Metformin was associated with reduced PCa risk in men with T2DM. This impact was enhanced by statins but reversed by finasteride. Metformin, statins, and finasteride are potential PCa prevention agents. The interaction of these drugs on PCa risk needs further confirmation in other cohorts. Our finding of differential impacts of metformin, statins, and finasteride (alone or in combination) on PCa risk is informative for treatment management in men at risk for PCa and T2DM.

The association of cardioprotective medications with pneumonia-related outcomes.

INTRODUCTION: Little research has examined whether cardiovascular medications, other than statins, are associated with improved outcomes after pneumonia. Our aim was to examine the association between the use of beta-blockers, statins, angiotensin converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs) with pneumonia-related outcomes. MATERIALS AND METHODS: We conducted a retrospective population-based study on male patients ≥ 65 years of age hospitalized with pneumonia and who did not have pre-existing cardiac disease. Our primary analyses were multilevel regression models that examined the association between cardiovascular medication classes and either mortality or cardiovascular events. RESULTS: Our cohort included 21,985 patients: 22% died within 90 days of admission, and 22% had a cardiac event within 90 days. The cardiovascular medications studied that were associated with decreased 90-day mortality included: statins (OR 0.70, 95% CI 0.63-0.77), ACE inhibitors (OR 0.82, 95% CI 0.74-0.91), and ARBs (OR 0.58, 95% CI 0.44-0.77). However, none of the medications were significantly associated with decreased cardiovascular events. DISCUSSION: While statins, ACE inhibitors, and ARBs, were associated with decreased mortality, there was no significant association with decreased CV events. These results indicate that this decreased mortality is unlikely due to their potential cardioprotective effects.

Very low levels of atherogenic lipoproteins and the risk for cardiovascular events: a meta-analysis of statin trials.

BACKGROUND: Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease risk is not well-documented. OBJECTIVES: The aim of this meta-analysis was to evaluate: 1) the interindividual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB) levels achieved with statin therapy; 2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy; and 3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and cardiovascular disease risk. METHODS: This meta-analysis used individual patient data from 8 randomized controlled statin trials, in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. RESULTS: Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large interindividual variability in the reductions of LDL-C, non-HDL-C, and apoB achieved with a fixed statin dose. More than 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target <70 mg/dl. Compared with patients who achieved an LDL-C >175 mg/dl, those who reached an LDL-C 75 to <100 mg/dl, 50 to <75 mg/dl, and <50 mg/dl had adjusted hazard ratios for major cardiovascular events of 0.56 (95% confidence interval [CI]: 0.46 to 0.67), 0.51 (95% CI: 0.42 to 0.62), and 0.44 (95% CI: 0.35 to 0.55), respectively. Similar associations were observed for non-HDL-C and apoB. CONCLUSIONS: The reductions of LDL-C, non-HDL-C, and apoB levels achieved with statin therapy displayed large interindividual variation. Among trial participants treated with high-dose statin therapy, >40% did not reach an LDL-C target <70 mg/dl. Patients who achieve very low LDL-C levels have a lower risk for major cardiovascular events than do those achieving moderately low levels.

Assessing appropriateness of lipid management among patients with diabetes mellitus: moving from target to treatment.

BACKGROUND: Performance measures that emphasize only a treat-to-target approach may motivate overtreatment with high-dose statins, potentially leading to adverse events and unnecessary costs. We developed a clinical action performance measure for lipid management in patients with diabetes mellitus that is designed to encourage appropriate treatment with moderate-dose statins while minimizing overtreatment. METHODS AND RESULTS: We examined data from July 2010 to June 2011 for 964 818 active Veterans Affairs primary care patients ≥18 years of age with diabetes mellitus. We defined 3 conditions as successfully meeting the clinical action measure for patients 50 to 75 years old: (1) having a low-density lipoprotein (LDL) <100 mg/dL, (2) taking a moderate-dose statin regardless of LDL level or measurement, or (3) receiving appropriate clinical action (starting, switching, or intensifying statin therapy) if LDL is ≥100 mg/dL. We examined possible overtreatment for patients ≥18 years of age by examining the proportion of patients without ischemic heart disease who were on a high-dose statin. We then examined variability in measure attainment across 881 facilities using 2-level hierarchical multivariable logistic models. Of 668 209 patients with diabetes mellitus who were 50 to 75 years of age, 84.6% passed the clinical action measure: 67.2% with LDL <100 mg/dL, 13.0% with LDL ≥100 mg/dL and either on a moderate-dose statin (7.5%) or with appropriate clinical action (5.5%), and 4.4% with no index LDL on at least a moderate-dose statin. Of the entire cohort ≥18 years of age, 13.7% were potentially overtreated. Facilities with higher rates of meeting the current threshold measure (LDL <100 mg/dL) had higher rates of potential overtreatment (P<0.001). CONCLUSIONS: Use of a performance measure that credits appropriate clinical action indicates that almost 85% of diabetic veterans 50 to 75 years of age are receiving appropriate dyslipidemia management. However, many patients are potentially overtreated with high-dose statins.