Statin dose titration patterns and subsequent major cardiovascular events in very high-risk patients: estimates from Swedish population-based registry data

2020 ◽  
Vol 6 (4) ◽  
pp. 323-331
Author(s):  
Jonas Banefelt ◽  
Maria Lindh ◽  
Maria K Svensson ◽  
Björn Eliasson ◽  
Ming-Hui Tai
Keyword(s):  
High Risk ◽  
Statin Therapy ◽  
High Intensity ◽  
Lower Risk ◽  
Cardiovascular Events ◽  
Population Based ◽  
Moderate Intensity ◽  
Risk Patients ◽  
Population Based Registry ◽  
Very High

Abstract Aims Clinical studies have demonstrated the efficacy of intensive statin therapy in lowering low-density lipoprotein cholesterol and cardiovascular (CV) events. Our objective was to examine statin titration patterns and the association between titration patterns and subsequent CV events in very high-risk patients. Methods and results Using Swedish national population-based registry data, we identified 192 435 patients with very high risk of atherosclerotic CV disease initiated on moderate-intensity statin therapy between 2006 and 2013. Outcomes of interest were titration to high-intensity therapy and the major adverse cardiovascular events (MACE) composite (myocardial infarction, ischaemic stroke, and CV death) outcome. Cumulative incidence of MACE was assessed by titration status 1-year post-treatment initiation in patients adherent to treatment during the first year, using a 12-week cut-off from initiation to define early, delayed and no up-titration to high-intensity statins. Cox regression analysis was used to estimate adjusted hazard ratios (HRs). In 144 498 eligible patients, early titration was associated with significantly lower risk of MACE in the subsequent 2 years compared to no up-titration (HR 0.76, P < 0.01]. Delayed up-titration was associated with a smaller reduction (HR 0.88, P = 0.08). The majority of patients did not up-titrate. Conclusion Early up-titration to high-intensity statins was independently associated with lower risk of subsequent CV events compared to no up-titration. Delayed up-titration was not associated with the same benefit. Despite the higher risk associated with no up-titration, few patients at very high CV risk who started treatment on moderate-intensity up-titrated to high intensity, indicating a potential need for more aggressive lipid management of these patients in clinical practice.

scholarly journals High risk US adults with untreated hyperlipidaemia in NHANES: estimated reduction in cardiovascular events with statin treatment

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
P.P Toth ◽  
M.K Palmer
Keyword(s):  
High Risk ◽  
Statin Therapy ◽  
High Intensity ◽  
Statin Treatment ◽  
Moderate Intensity ◽  
High Dose ◽  
High Risk Patients ◽  
Chd Risk ◽  
The Us ◽  
Risk Patients

Abstract Introduction Dyslipidemia is widely prevalent. Despite guidelines that recommend statin therapy for high-risk patients, many of these patents are untreated. This gap in care must be urgently closed. Purpose We analyzed data from the National Health and Nutrition Examination Survey (NHANES) in order to: (1) ascertain the number of high-risk individuals with dyslipidaemia not receiving lipid lowering therapy in the United States; and (2) estimate the reduction in acute cardiovascular (CV) events if those individuals were treated with either moderate or high potency statins in order to achieve at minimum a 30% or 50% reduction in LDL-C levels. Methods Data from NHANES participants who had fasting blood serum data available, including lipids, were included in our analysis (n=14,888). Statistical analyses were performed in the R language. Coronary heart disease (CHD) risk was assessed using NCEP ATP III criteria, and participants were categorized as being at high, intermediate, or low CHD risk. Data from seven surveys from 2003–4 to 2015–6 was used and extrapolations to the US adult population (50 states plus the District of Columbia) were performed using the direct method to the US Census 2000 population. Results We identified 1162 adults (age 20–79) who were high-risk and untreated despite being hyperlipidaemic (LDLC ≥100mg/dL). We estimated they represent 12.8 million individuals in the US 2015–16 population. Without lipid modification and hypothecating 10-year risks of CV events in this group of 20, 25, 30, 35 and 40%, respectively, predicted numbers of CV events are 2.6M, 3.2M, 3.9M, 4.5M, and 5.1M. Moderate-intensity statins reduce LDLC by 30–40% and high-intensity statins by 50–60%. Using untreated LDL-C values from all NHANES surveys we calculated predicted absolute reductions in LDL-C would be at least 42 mg/dL if a moderate-intensity statin was used and at least 70 mg/dL if a high-intensity statin was used, with reductions in CV risk of at least 27% and 46%, respectively. In this group of untreated high-risk individuals, predicted numbers of CV events that could be prevented by moderate-intensity statin for 10 years range from at least 0.7M to at least 1.4M, and with high-intensity statin use for 10 years from at least 1.2M to at least 2.3M, depending on the level of untreated risk. With Numbers Needed to Treat (NTT) between 5 and 18, use of statin treatment in this group would be highly beneficial and cost-effective. Conclusions There are a large number of untreated high-risk individuals with dyslipidaemia in the US. Use of moderate and high dose statin therapy in these patients for 10 years would reduce CV risk by at least 27% and 47%, respectively. Among untreated high-risk patients, the NNTs for moderate and high dose statin therapy are 9–18 and 5–11, respectively, depending on 10-year level of CV risk. The quality of life and socioeconomic implications of these estimates are substantial. Funding Acknowledgement Type of funding source: None

Disease Response Guiding Therapy in Acute Lymphocytic Leukemia: Pivotal Role of Minimal Residual Disease

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. SCI-34-SCI-34
Author(s):  
Michael A. Pulsipher
Keyword(s):  
Flow Cytometry ◽  
High Risk ◽  
Minimal Residual Disease ◽  
Lower Risk ◽  
Residual Disease ◽  
Response To Therapy ◽  
Risk Patients ◽  
Very High ◽  
Minimal Residual ◽  
Risk Of Relapse

In spite of an explosion of data regarding mutations associated with childhood ALL, to date these key genetic changes rarely have been the driver of therapy. Clinical parameters at presentation (WBC, age, T- vs. B-lineage, etc.) have dictated initial risk stratification and induction approaches, followed by risk-adapted therapy based upon leukemic response measured by minimal residual disease (MRD, either PCR- or flow cytometry-based). With minor variations, rapid disappearance of peripheral MRD, followed by significant clearance from the marrow after induction, and most importantly, the level of MRD after consolidation have allowed clear distinctions in outcomes that have driven intensification or de-intensification of therapy resulting in improved outcomes. Although specific gene mutations have been associated with risk, MRD has further identified better risk patients within genetic subgroups. For patients noted to be very high risk who are candidates for hematopoietic cell transplantation (HCT), the presence of MRD both pre- and post-transplant has been associated with increased risk of relapse; the risk being modified by level of MRD, whether or not GVHD occurs after HCT, and timing after HCT when MRD is measured. In lower risk patients being treated with chemotherapy and higher risk patients eligible for HCT, more sensitive approaches to flow cytometry and PCR, as well as next-generation sequencing (NGS) MRD approaches (sensitive to 1/10^7 cells) are currently being tested. It is not clear yet whether NGS-MRD offers substantial improvements in patients treated with chemotherapy, as broad-based testing is underway; the latest comparative outcomes will be presented. There is evidence of a striking improvement in our ability to define patients who will do very will after transplant (not relapse), and preliminary evidence that post-HCT NGS MRD testing is more sensitive that other methodologies in defining risk of relapse after transplant. As the latest information about the ability of different approaches to MRD is shown in this session, we will also present how response to therapy based upon MRD interacts with various genetic subtypes (Ph+ ALL, extreme hypodiploidy, etc.). Even in subclasses that are considered very high risk based solely upon genetics, measurement of MRD can define higher and lower risk groups. Going forward, as more and different types of patients are subcategorized and treated with targeted agents based upon specific mutations, it is likely MRD response will continue to be important in mapping intensity of approach and defining children at highest risk of relapse who might benefit from HCT or other cellular therapeutic approaches. Disclosures Pulsipher: Novartis: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Assessment of statin therapy, LDL-C levels, and cardiovascular events among high-risk patients in the United States

2016 ◽  
Vol 10 (1) ◽  
pp. 63-71.e3 ◽  
Author(s):  
Sudhir K. Unni ◽  
Ruben G.W. Quek ◽  
Joseph Biskupiak ◽  
Vinson C. Lee ◽  
Xiangyang Ye ◽  
...  
Keyword(s):  
United States ◽  
High Risk ◽  
Statin Therapy ◽  
Cardiovascular Events ◽  
The United States ◽  
High Risk Patients ◽  
Risk Patients

scholarly journals Statins for primary prevention of cardiovascular disease: modelling guidelines and patient preferences based on an Irish cohort

2019 ◽  
Vol 69 (683) ◽  
pp. e373-e380 ◽  
Author(s):  
Paula Byrne ◽  
John Cullinan ◽  
Paddy Gillespie ◽  
Rafael Perera ◽  
Susan M Smith
Keyword(s):  
Cardiovascular Disease ◽  
Primary Prevention ◽  
High Risk ◽  
Statin Therapy ◽  
Clinical Guidelines ◽  
Baseline Risk ◽  
Recommended Treatment ◽  
Risk Patients ◽  
Very High ◽  
Prevention Of Cardiovascular Disease

BackgroundChanges in clinical guidelines for primary prevention of cardiovascular disease (CVD) have widened eligibility for statin therapy.AimTo illustrate the potential impacts of changes in clinical guidelines.Design and settingModelling the impacts of seven consecutive European guidelines based on a cohort of people aged ≥50 years from the Irish Longitudinal Study on Ageing.MethodThe eligibility for statin therapy of a sample of people without a history of CVD was established, according to changing guideline recommendations and modelled associated potential costs. The authors calculated the numbers needed to treat (NNT) to prevent one major vascular event in patients at the lowest baseline risk for which each of the seven guidelines recommended treatment, and for those at low, medium, high, and very-high risk according to 2016 guidelines. These were compared with the NNT that patients reported as required to justify taking a daily medicine.ResultsThe proportion of patients eligible for statins increased from approximately 8% in 1987 to 61% in 2016; associated costs rose from €13.9 million to €107.1 million per annum. The NNT for those at the lowest risk for which each guideline recommended treatment rose from 40 to 400. By 2016, the NNT for low-risk patients was 400 compared to ≤25 very-high risk patients. The proportion of patients eligible for statins achieving NNT levels that patients regarded as justified to taking a daily medicine fell as guidelines changed over time.ConclusionIncreased eligibility for statin therapy impacts large proportions of the present population and healthcare budgets. Decisions to take and reimburse statins should be considered on the basis of expected cost-effectiveness and acceptability to patients.

P643Association of adherence and treatment intensity of lipid-lowering therapy with cardiovascular outcomes and all-cause mortality in very high-risk patients in Germany

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Khachatryan ◽  
B Monga ◽  
E Sidelnikov ◽  
M Hatz ◽  
I Ahrens
Keyword(s):  
High Risk ◽  
Lower Risk ◽  
Cardiovascular Outcomes ◽  
Lipid Lowering ◽  
Study Endpoint ◽  
Treatment Intensity ◽  
High Risk Patients ◽  
All Cause Mortality ◽  
Risk Patients ◽  
Very High

Abstract Introduction Both intensity and adherence to lipid lowering therapies (LLT) play an important role in effectiveness of the therapies in patients at risk for cardiovascular events. Purpose To evaluate the association of adherence and treatment intensity with cardiovascular outcomes and all-cause mortality in very high-risk patients (as defined by the current ESC guidelines) treated with statin and/or ezetimibe. Methods Retrospective cohort study was based on German health claims data (2010–2015) obtained from German Institute for Health Research (InGef) database and included patients ≥18 years with an initial LLT treatment (statin and/or ezetimibe) in 2011–2013, and diagnoses of cardiovascular disease (CVD), stage 4 or 5 chronic kidney disease (CKD) or type 2 diabetes mellitus (DM). Patients must have had at least 2 LLT prescriptions in the first year to ensure intention of treatment. Follow-up period started 1 year after the second LLT prescription and continued until one of the events of the composite study endpoint (hospitalisation for myocardial infarction, unstable angina, ischemic stroke, heart failure, revascularization, or all-cause death) or 31.12.2015, whichever occurred earlier. Adherence was measured annually by the proportion of days covered (PDC) using prescription data. Treatment intensity was quantified based on expected LDL-C reduction as described in the American College of Cardiology and American Heart Association (ACC/AHA) 2018 guidelines. Adherence and treatment intensity were multiplied to create a combined measure of intensity after accounting for adherence. Results 73,257 patients of the CVD cohort were 68 (SD=12) years old, 59% men; the DM cohort (no CVD) had 13,584 patients, age 64 (10), 47% men; 472 patients in the CKD cohort (no CVD) were 65 (15) years old, 46% men. In a Cox proportional hazards model, each 10% increase in treatment intensity (LDL-C lowering) was associated with 18% lower risk of CV event in the CVD (HR 0.82, 95% CI 0.82–0.83), 21% - in the DM (HR 0.79, 95% CI 0.76–0.83), and 15% - in the CKD (HR 0.85, 95% CI 0.75–0.97) cohorts. Similarly, each 10% increase in adherence (PDC) was associated with 6% lower risk of CV event in the CVD (HR 0.94, 95% CI 0.93–0.94), 7% - in the DM (HR 0.93, 95% CI 0.91–0.94), and 7% - in the CKD (HR 0.93, 95% CI 0.89–0.97) cohorts. Each 10% increase in adherence-adjusted intensity was associated with 16% lower risk of CV event in the CVD (HR 0.84, 95% CI 0.83 - 0.85), 19% - in the DM (HR 0.81, 95% CI 0.78–0.85), and 17% - in the CKD (HR 0.83, 95% CI 0.72–0.96) cohorts. The models controlled for age, sex, Charlson comorbidity index and other cardiovascular risk factors at baseline. Conclusions A higher adherence and/or treatment intensity of LLT was associated with significantly lower risk of CV outcomes or all-cause death in German very high-risk patients. Strategies to tailor intensity to patient profile and improve adherence could further lower risk of CV events. Acknowledgement/Funding Amgen Europe GmbH

Identification of Poor Risk Patients in Low and Intermediate-1 (Int-1) IPSS MDS with the New Ipssr Index and Comparison with Other Prognostic Indexes. A Study by the Spanish Group of MDS (GESMD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 702-702 ◽  
Author(s):  
David Valcárcel ◽  
Guillermo Sanz ◽  
Margarita Ortega ◽  
Benet Nomdedeu ◽  
Elisa Luño ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lower Risk ◽  
Poor Prognosis ◽  
Median Overall Survival ◽  
Poor Risk ◽  
Number Of Patients ◽  
Risk Patients ◽  
Md Anderson ◽  
Very High

Abstract Abstract 702 Despite that low and intermediate-1 (int-1) IPSS groups are commonly considered as low risk diseases with a median overall survival exceeding 60 months, some of these patients will evolve as higher risk myelodysplastic syndrome (MDS). Recently several new prognosis indexes (PI) have been proposed: The new IPSSr, WPSSr, MD Anderson for lower risk patients (MDA) Index, and the Spanish Group of MDS (GESMD) proposal that considers as high risk those patients with int-1 IPSS and at least one of the following: platelets <30×109/L, granulocytes <0.5×109/L, poor or very poor-risk karyotype or the presence of bone marrow (BM) fibrosis. The aim of the study was to compare the four PI and to analyze which of them was the best to identify patients with the poorest risk (defined as those with a median overall survival (OS) lower than 30 months) and to segregate different risk groups in a population of lower risk MDS patients. Indexes were compared using the Akaike analysis methodology. A total of 2410 patients from the Spanish registry of MDS with low or int-1 IPSS were included. Median age was 74 years (42.6% female). The IPSS value was of: 0, 0.5 and 1 in 1314, 761 and 335 patients, respectively. The four poor risk variables defined by the GESMD confirmed its adverse predictive value for OS: granulocytes <0.5×109/L (n=101, P<0.001), platelets <30×109/L (n=94, P<0.001), poor or very poor risk karyotype (n=35, P=0.007), and BM fibrosis (n=109 of 698 evaluable patients, P<0.001). The presence of at least one of these was associated with adverse prognosis in the int-1 group but not in the low IPSS risk group, thus only the former was considered as high risk. The distribution of patients across the four PI is detailed in the Table. These new PI identified between 16.9% and 46% of patients having a median OS of around 30 months within the int-1 patients (wide line in the table), but none of the PIs could identify such a poor prognosis patients in the low IPSS group. The PI that identified the highest number of patients with shorter OS was the new IPSSr, while MDA IP was the most discriminative in the Akaike analysis. In conclusion, IPSS is not discriminative enough in the int-1 group. In contrast, the application of the new PI can be employed to better identify poor prognosis patients within the int-1 group who could benefit from a high-risk approach. Table. Overall survival and AML evolution according to the different prognostic index. PROGNOSIS INDEX (AIC for the whole population/and for the Int-1) populations) PROGNOSIS GROUP IPSS LOW (N=1314) OS: 87.78 m (95% CI:74.5-101.0) AML EVOLUTION (3 years): 9.1% (95% CI: 6.9-11.3%) IPSS INT-1 (N= 1096) OS: 44.2 m (95% CI:39.1-49.3) AML EVOLUTION (3 years): 26.9% (95% CI: 23-30.8%) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) N (%) Overall Survival Median (95% CI) months AML evolution (3 years) % (95% CI) GESMD (12566.6/6425.9) LOW 1314 (100) 860 (78.5) 48.1 (40.9-55.3)* 25.1 (20.7-29.5)** HIGH 0 (0) 236 (21.5) 32.7 (39.1-49.3)* 34.3 (24.5-44.1)** MD. Anderson (12381.4/6357.2) LOW 508 (39.3) 130.3 (104.6-157.0)* 9% (5.4-12.6)! 109 (9.9) 115.2 (83.8-146.6)* 15.7 (6.5-24.9)* INT 781 (59.4) 69.7 (62.4-77.1)* 8.9% (6.9-11.9)! 653 (59.6) 51.3 (44.2-58.3)* 23.3 (18.3-28.3)* HIGH 25 (1.9) 58.4* (25.4-91.5)* ——–——–— 334 (30.5) 24.1 (19.3-28.9)* 39.9 (31.3-48.5)* IPSS-R (12409.9/6369.6) VERY LOW 690 (52.5) 118.8 (105.7-131.7)* 6.4% (4.2-8.6)*** 79 (7.2) 113.7 (39.9-187.4)* 17.8 (4.6-31)* LOW 602 (45.8) 65.9 (57.6-74.2)* 11.6% (7.8-15.4)*** 505 (46.1) 60.3 (53.3-67.2)* 18.2 (13.4-23)* INT 22 (1.7) 58.9 (25.2-92.7)* 26% (2-50)*** 416 (38) 30.5 (26.1-34.8)* 38.6 (30-47.2)* HIGH 0 (0) 95 (8.7) 21.2 (16.5-25.9)* 48.5 (32.5-64.5)* VERY HIGH 0 (0) 1 (0.1) WPSS-R (12477.4/6414.7) VERY LOW 517 (39.3) 115.2 (103.0-127.4)* 6.5 (3.7-9.3)$ 76 (6.9) 56.5 (38.2-74.9)* 22.8 (10.6-35)* LOW 524 (39.9) 78.5 (66.7-90.3)* 12.1 (7.7-15.5)$ 289 (26.4) 61.3 (48.3-74.2)* 19.2 (12.4-25.6)* INT 61 (4.6) 46.0 (30.8-61.1)* 13.7 (3.1-24.3)$ 386 (5.2) 42.5 (32.8-52.2)* 27.8 (20.8-34.8)* HIGH 3 (0.2) 185 (16.9) 24.11 (19.4-28.8)* 49.3 (35.7-62.9)* VERY HIGH 0 (0) 4 (0.4) NOT EVAL 209 (15.9) 87.8 (74.6-101.3)* 7.2 (3-11.4)$ 156 (14.2) 48 (30.8-65.2) 18.3 (9.1-27.5)* AIC: Akaike Information Criteria. Int: Intermediate, Not Eval: Not evaluable, CI: Confidence interval. * P<0.001; ** P=0.02; *** P=0.04; ! !P=0.7 $P=0.1 Figure. Actuarial curves of overall survival according to the different PI. Figure. Actuarial curves of overall survival according to the different PI. Disclosures: No relevant conflicts of interest to declare.

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