Association Between Diagnosis-to-Limb Revascularization Time and Clinical Outcomes in Outpatients With Chronic Limb-Threatening Ischemia: Insights From the CLIPPER Cohort.

BACKGROUND: The extent and consequences of ischemia in patients with chronic limb-threatening ischemia (CLTI) may change rapidly, and delays from diagnosis to revascularization may worsen outcomes. We sought to describe the association between time from diagnosis to endovascular lower extremity revascularization (diagnosis-to-limb revascularization [D2L] time) and clinical outcomes in outpatients with CLTI. METHODS AND RESULTS: In the CLIPPER cohort, comprising patients between 66 and 86 years old diagnosed with CLTI betweeen 2010 and 2019, we used Medicare claims data to identify patients who underwent outpatient endovascular revascularization within 180 days of diagnosis. We described the risk-adjusted association between D2L time and clinical outcomes. Among 1 130 065 patients aged between 66 and 86 years with CLTI, 99 221 (8.8%) underwent outpatient endovascular lower extremity revascularization within 180 days of their CLTI diagnosis. Among patients with D2L time <30 days, there was no association between D2L time and all-cause death or major lower extremity amputation. However, among patients with D2L time >30 days, each additional 10-day increase in D2L time was associated with a 2.5% greater risk of major amputation (hazard ratio, 1.025 [95% CI, 1.014-1.036]). There was no association between D2L time and all-cause death. CONCLUSIONS: A delay of >30 days from CLTI diagnosis to lower extremity endovascular revascularization was associated with an increased risk of major lower extremity amputation among patients undergoing outpatient endovascular revascularization. Improving systems of care to reduce D2L time could reduce amputations.

Gamification-augmented home-based exercise for peripheral artery disease: Rationale and design of the GAMEPAD Study.

BACKGROUND: Supervised exercise therapy improves walking performance, functional capacity, and quality of life in patients with peripheral artery disease (PAD). However, few patients with PAD are enrolled in supervised exercise programs, and there are a number of logistical and financial barriers to their participation. A home-based walking intervention is likely to be more accessible to patients with PAD, but no fully home-based walking program has demonstrated efficacy. Concepts from behavioral economics have been used to design scalable interventions that increase daily physical activity in patients with atherosclerotic vascular disease, but whether a similar program would be effective in patients with PAD is uncertain. STUDY DESIGN AND OBJECTIVES: GAMEPAD (NCT04536012) is a pragmatic, virtual, randomized controlled trial designed to evaluate the effectiveness of a gamification strategy informed by concepts from behavioral economics to increase daily physical activity in patients with PAD who are seen in cardiology and vascular surgery clinics affiliated with the University of Pennsylvania Health System. Patients are contacted by email or text message, and complete enrollment and informed consent on the Penn Way to Health online platform. A GAMEPAD substudy will evaluate the effectiveness of opt-in versus opt-out framing when approaching patients for study participation. Patients are then provided with a wearable fitness tracker, establish a baseline daily step count, set a goal to increase daily step count by 33%-50%, and are randomized 1:1 to the gamification or control arms. Interventions continue for 16 weeks, including a 4-week period during which goal step count is gradually increased in the gamification arm, with follow-up for an additional 8 weeks to evaluate the durability of behavior change. The trial has met its enrollment goal of 102 participants, with a primary endpoint of change from baseline in daily steps over the 16-week intervention period. Key secondary endpoints include change from baseline in daily steps over the 8-week postintervention follow-up period and changes in patient-reported measures of PAD symptoms and quality of life over the intervention and follow-up periods. CONCLUSIONS: GAMEPAD is a virtual, pragmatic randomized clinical trial of a novel, fully home-based walking intervention informed by concepts from behavioral economics to increase physical activity and PAD-specific quality of life in patients with PAD. Its results will have important implications for the application of behavioral economic concepts to scalable home-based strategies to promote physical activity in patients with PAD and other disease processes where physical activity is limited by exertional symptoms. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov; NCT04536012.

Modelling Costs of Interventional Pulmonary Embolism Treatment: Implications of US Trends for a European Healthcare System.

BACKGROUND: Catheter-directed treatment (CDT) of acute pulmonary embolism (PE) is entering a growth phase in Europe following a steady increase in the United States (US) in the past decade, but the potential economic impact on European healthcare systems remains unknown. METHODS AND RESULTS: We built two statistical models for the monthly trend of proportion of CDT among patients with severe (intermediate- or high-risk) PE in the US. The conservative model was based on admission data from the National Inpatient Sample (NIS) 2016-2020, and the model reflecting increasing access to advanced treatment from the PERTTM national quality assurance database registry 2018-2021. By applying these models to the forecast of annual PE-related hospitalizations in Germany, we calculated the annual number of severe PE cases and the expected increase in CDT use for the period 2025-2030. The NIS-based model yielded a slow increase, reaching 3.1% (95% CI 3.0-3.2%) among all hospitalizations with PE in 2030; in the PERT-based model, increase would be steeper, reaching 8.7% (8.3-9.2%). Based on current reimbursement rates, we estimated an increase of annual costs for PE-related hospitalizations in Germany ranging from 15.3 to 49.8 million euros by 2030. This calculation does not account for potential cost savings, including those from reduced length of hospital stay. CONCLUSION: Our approach and results, which may be adapted to other European healthcare systems, provide a benchmark for healthcare costs expected to result from CDT. Data from ongoing trials on clinical benefits and cost savings are needed to determine cost-effectiveness and inform reimbursement decisions.

Contemporary Methods for Predicting Acute Kidney Injury After Coronary Intervention.

BACKGROUND: Acute kidney injury (AKI) is the most common complication after percutaneous coronary intervention (PCI). Accurately estimating patients' risks not only creates a means of benchmarking performance but can also be used prospectively to inform practice. OBJECTIVES: The authors sought to update the 2014 National Cardiovascular Data Registry (NCDR) AKI risk model to provide contemporary estimates of AKI risk after PCI to further improve care. METHODS: Using the NCDR CathPCI Registry, we identified all 2020 PCIs, excluding those on dialysis or lacking postprocedural creatinine. The cohort was randomly split into a 70% derivation cohort and a 30% validation cohort, and logistic regression models were built to predict AKI (an absolute increase of 0.3 mg/dL in creatinine or a 50% increase from preprocedure baseline) and AKI requiring dialysis. Bedside risk scores were created to facilitate prospective use in clinical care, along with threshold contrast doses to reduce AKI. We tested model calibration and discrimination in the validation cohort. RESULTS: Among 455,806 PCI procedures, the median age was 67 years (IQR: 58.0-75.0 years), 68.8% were men, and 86.8% were White. The incidence of AKI and new dialysis was 7.2% and 0.7%, respectively. Baseline renal function and variables associated with clinical instability were the strongest predictors of AKI. The final AKI model included 13 variables, with a C-statistic of 0.798 and excellent calibration (intercept = -0.03 and slope = 0.97) in the validation cohort. CONCLUSIONS: The updated NCDR AKI risk model further refines AKI prediction after PCI, facilitating enhanced clinical care, benchmarking, and quality improvement.

Implications of a Race Term in GFR Estimates Used to Predict AKI After Coronary Intervention.

BACKGROUND: The prediction of mortality, bleeding, and acute kidney injury (AKI) after percutaneous coronary intervention (PCI) traditionally relied on race-based estimates of the glomerular filtration rate (GFR). Recently, race agnostic equations were developed to advance equity. OBJECTIVES: The authors aimed to compare the accuracy and implications of various GFR equations when used to predict AKI after PCI. METHODS: Using the National Cardiovascular Data Registry (NCDR) CathPCI data set, we identified patients undergoing PCI in 2020 and calculated their AKI risk using the 2014 NCDR AKI risk model. We created 4 AKI models per patient for each estimate of baseline renal function: the traditional GFR equation with a race term, 2 GFR equations without a race term, and serum creatinine alone. We then compared each model's performance predicting AKI. RESULTS: Among 455,806 PCI encounters, the median age was 67 years, 32.2% were women, and 8.5% were Black. In Black patients, risk models without a race term were better calibrated than models incorporating an equation with a race term (intercept: -0.01 vs 0.15). Race-agnostic models reclassified 6% of Black patients into higher-risk categories, potentially prompting appropriate mitigation efforts. However, even with a race-agnostic model, AKI occurred in Black patients 18% more often than expected, which was not explained by captured patient or procedural characteristics. CONCLUSIONS: Incorporating a GFR estimate without a Black race term into the NCDR AKI risk prediction model yielded more accurate prediction of AKI risk for Black patients, which has important implications for reducing disparities and benchmarking.

Association of annual volume and in-hospital outcomes of catheter-directed thrombolysis for pulmonary embolism.

OBJECTIVE: We sought to evaluate the association between the institutional volume of catheter-directed thrombolysis (CDT) for pulmonary embolism and in-hospital mortality. BACKGROUND: CDT is an increasingly utilized therapy in patients with intermediate/high-risk PE. However, data on the relationship between hospital volume and clinical outcomes remain limited. METHODS: Patients who underwent CDT between October 1, 2015, and March 31, 2021, were identified in the Vizient Clinical Database. The primary outcome was in-hospital mortality. Secondary outcome were major complications, length of stay, and cost. Hospitals were dichotomized into <8 and ≥ 8 cases/year following restricted cubic spline analysis. RESULTS: A total of 6741 CDT procedures at 171 hospitals were included with a median annual hospital volume of 4.1 cases (IQR = 1.9-8.3). A total of 44 hospitals (25.7%) were classified as high-volume ( ≥ 8 cases/year) and performed 60.9% of all CDT cases. CDT at high-volume centers was associated with lower in-hospital mortality (6.0% vs. 11.3%; p < 0.0001). Stroke and bleeding rates were similar, but pulmonary complications were more frequent at low-volume centers. CDT at high volume centers was associated with a significantly shorter length of stay and lower cost. The association between high CDT volume and in-hospital mortality persisted after adjustment for demographics (odds ratio [OR] = 0.49, [0.41-0.58]), demographics and risk factors (OR = 0.52 [0.44-0.62]), and demographics, risk factors, and troponin elevation (OR = 0.51 [0.40-0.66]). CONCLUSION: In a large contemporary cohort of patients undergoing CDT in the United States, low annual institutional volume of CDT was associated with higher in-hospital mortality.

Risk factors for 30-day readmission in adults hospitalized for pulmonary hypertension.

Readmissions for pulmonary hypertension are poorly understood and understudied. We sought to determine national estimates and risk factors for 30-day readmission after pulmonary hypertension-related hospitalizations. We utilized the Healthcare Cost and Utilization Project Nationwide Readmission Database, which has weighted estimates of roughly 35 million discharges in the US. Adult patients with primary International Classification of Disease, Ninth Revision, Clinical Modification diagnosis codes of 416.0 and 416.8 for primary and secondary pulmonary hypertension with an index admission between 2012 and 2014 and any readmission within 30 days of the index event were identified. Predictors of 30-day readmission were identified using multivariable logistic regression with adjustment for covariates. Results showed that the national estimate for Primary Pulmonary Hypertension vs Secondary Pulmonary Hypertension-related index events between 2012 and 2014 with 30-day readmission was 247 vs 2550 corresponding to a national readmission risk estimate of 17% vs 18.3%, respectively. The presence of fluid and electrolyte disorders, renal failure, and alcohol abuse were associated with increased risk of readmission in Primary Pulmonary Hypertension, while factors associated with Secondary Pulmonary Hypertension readmissions included anemia, congestive heart failure, lung disease, fluid and electrolyte disorders, renal failure, diabetes, and liver disease. The median cost of Primary Pulmonary Hypertension admissions and readmissions were $46,132 (IQR: $25,384-$85,647) and $41,604.50 (IQR: $22,481.50-$84,420.50), respectively. The median costs of Secondary Pulmonary Hypertension admissions and readmissions were $34,893 (IQR: $19,670-$66,143) and $36,279 (IQR: $19,059-$74,679), respectively. In conclusion, approximately 19% of Primary Pulmonary Hypertension and Secondary Pulmonary Hypertension hospitalizations result in 30-day readmission, with significant costs accrued during the index hospitalization and readmission. With evolving clinical terminology and diagnostic codes, future study will need to better clarify underlying factors associated with readmissions amongst pulmonary hypertension sub-types, and identify methods and procedures to minimize readmission risk.

Diagnosis and Treatment of Pulmonary Embolism During the Coronavirus Disease 2019 Pandemic: A Position Paper From the National PERT Consortium.

The coexistence of coronavirus disease 2019 (COVID-19) and pulmonary embolism (PE), two life-threatening illnesses, in the same patient presents a unique challenge. Guidelines have delineated how best to diagnose and manage patients with PE. However, the unique aspects of COVID-19 confound both the diagnosis and treatment of PE, and therefore require modification of established algorithms. Important considerations include adjustment of diagnostic modalities, incorporation of the prothrombotic contribution of COVID-19, management of two critical cardiorespiratory illnesses in the same patient, and protecting patients and health-care workers while providing optimal care. The benefits of a team-based approach for decision-making and coordination of care, such as that offered by pulmonary embolism response teams (PERTs), have become more evident in this crisis. The importance of careful follow-up care also is underscored for patients with these two diseases with long-term effects. This position paper from the PERT Consortium specifically addresses issues related to the diagnosis and management of PE in patients with COVID-19.

Mid-term outcomes with the use of extracorporeal membrane oxygenation for cardiopulmonary failure secondary to massive pulmonary embolism.

OBJECTIVES: There has been increasing interest in using extracorporeal membrane oxygenation (ECMO) to rescue patients with pulmonary embolism (PE) in the advanced stages of respiratory or haemodynamic decompensation. We examined mid-term outcomes and risk factors for in-hospital mortality. METHODS: We conducted a retrospective study of 36 patients who required ECMO placement (32 veno-arterial ECMO, 4 veno-venous) following acute PE. Survival curves were estimated using the Kaplan-Meier method. Risk factors for in-hospital mortality were assessed by logistic regression analysis. Functional status and quality of life were assessed by phone questionnaire. RESULTS: Overall survival to hospital discharge was 44.4% (16/36). Two-year survival conditional to discharge was 94% (15/16). Two-year survival after veno-arterial ECMO was 39% (13/32). In patients supported with veno-venous ECMO, survival to discharge was 50%, and both patients were alive at follow-up. In univariable analysis, a history of recent surgery (P = 0.064), low left ventricular ejection fraction (P = 0.029), right ventricular dysfunction ≥ moderate at weaning (P = 0.083), on-going cardiopulmonary resuscitation at ECMO placement (P = 0.053) and elevated lactate at weaning (P = 0.002) were risk factors for in-hospital mortality. In multivariable analysis, recent surgery (P = 0.018) and low left ventricular ejection fraction at weaning (P = 0.013) were independent factors associated with in-hospital mortality. At a median follow-up of 23 months, 10 patients responded to our phone survey; all had acceptable functional status and quality of life. CONCLUSIONS: Massive acute PE requiring ECMO support is associated with high early mortality, but patients surviving to hospital discharge have excellent mid-term outcomes with acceptable functional status and quality of life. ECMO can provide a stable platform to administer other intervention with the potential to improve outcomes. Risk factors for in-hospital mortality after PE and veno-arterial ECMO support were identified.

Outcomes of catheter-directed versus systemic thrombolysis for the treatment of pulmonary embolism: A real-world analysis of national administrative claims.

Catheter-directed thrombolysis (CDT) and systemic thrombolysis (ST) are used to treat intermediate/high-risk pulmonary embolism (PE) in the absence of comparative safety and effectiveness data. We utilized a large administrative database to perform a comparative safety and effectiveness analysis of catheter-directed versus systemic thrombolysis. From the Optum® Clinformatics® Data Mart private-payer insurance claims database, we identified 100,744 patients hospitalized with PE between 2004 and 2014. We extracted demographic characteristics, high-risk PE features, components of the Elixhauser Comorbidity Index, and outcomes including intracranial hemorrhage (ICH), all-cause bleeding, and mortality among all patients receiving CDT and ST. We used propensity score methods to compare outcomes between matched cohorts adjusted for observed confounders. A total of 1915 patients (1.9%) received either CDT (n = 632) or ST (n = 1283). Patients in the CDT group had fewer high-risk features including less shock (5.4 vs 11.1%; p < 0.001) and cardiac arrest (6.8 vs 11.0%; p = 0.004). In 1:1 propensity-matched groups, ICH rates were 1.9% in both the CDT and ST groups (p = 1.0). All-cause bleeding was higher in the CDT group (15.9 vs 8.7%; p < 0.001), while in-hospital mortality was lower (6.5 vs 10.0%; p = 0.02). Among a nationally representative cohort of patients with PE at higher risk for mortality, CDT was associated with similar ICH rates, increased all-cause bleeding, and lower short and intermediate-term mortality when compared with ST. The competing risks and benefits of CDT in real-world practice suggest the need for large-scale randomized clinical trials with appropriate comparator arms.

Presence of Contralateral Carotid Occlusion Is Associated With Increased Periprocedural Stroke Risk Following CEA but Not CAS: A Meta-analysis and Meta-regression Analysis of 43 Studies and 96,658 Patients.

Purpose: To investigate the prognostic role of contralateral carotid artery occlusion (CCO) in perioperative outcomes of patients undergoing carotid artery endarterectomy (CEA) vs carotid artery stenting (CAS). Materials and Methods: The PubMed, Scopus, and Cochrane databases were searched up to September 2018 to identify observational or randomized studies that compared outcomes of carotid revascularization in patients with vs without CCO. Forty-three studies (46 arms) comprising 96,658 patients were selected (75,857 CEA and 20,801 CAS). The CCO group included 9258 patients. Heterogeneity was assessed with the Higgins I2 test. I2>75% indicated significant heterogeneity. A random effects model was used to account for heterogeneity among studies. The results were reported as the odds ratios (ORs) with the 95% confidence intervals (CIs). Meta-regression analysis examined potential confounders. Publication bias was quantified by the Egger method. Results: Carotid revascularization in patients with CCO was associated with an increased risk of 30-day mortality (OR 1.75, 95% CI 1.38 to 2.23, p<0.001; I2=0%), stroke (OR 1.77, 95% CI 1.41 to 2.22, p<0.001; I2=46%), transient ischemic attack (TIA) (OR 2.10, 95% CI 1.34 to 3.27, p=0.001; I2=15%), and the composite endpoint of stroke/death (OR 1.78, 95% CI 1.54 to 2.05, p<0.001; I2=0%). No difference was noted in the risk of perioperative myocardial infarction (OR 0.81, 95% CI 0.50 to 1.31; p=0.388; I2=0%). Subgroup analysis demonstrated that CEA in patients with CCO was associated with an increased risk of stroke (OR 2.07, 95% CI 1.72 to 2.49, p<0.001; I2=14%), death (OR 1.80, 95% CI 1.55 to 2.10, p<0.001; I2=0%), TIA (OR 2.18, 95% CI 1.38 to 3.45, p<0.001; I2=13%), and stroke/death (OR 1.80, 95% CI 1.55 to 2.10, p<0.001; I2=0%), whereas CCO patients who were treated with CAS were at an increased risk for death (OR 1.65, 95% CI 1.07 to 2.60, p=0.023; I2=0%) but not stroke (OR 0.94, 95% CI 0.61 to 1.47; p=0.080; I2=31%) or TIA (OR 1.18, 95% CI 0.18 to 7.55; p=0.861; I2=43%). The meta-regression analysis did not find any significant association for any of the outcomes, and there was no evidence of publication bias. Conclusion: Carotid revascularization outcomes are adversely affected by the presence of CCO. Patients with CCO have a significantly higher risk of periprocedural stroke, death, and TIA. CEA in patients with CCO is associated with an increased risk of perioperative stroke, death, TIA, and death/stroke, while CAS in the presence of a CCO is associated with an increased risk of periprocedural death but not stroke or TIA.

Use, Safety and Effectiveness of Subintimal Angioplasty and Re-Entry Devices for the Treatment of Femoropopliteal Chronic Total Occlusions: A Systematic Review of 87 Studies and 4,665 Patients.

BACKGROUND: Subintimal angioplasty (SIA) is often utilized to cross femoropopliteal (FP) artery chronic total occlusions (CTOs). Re-entry devices (RED) can further assist with true lumen re-entry. OBJECTIVE: To systematically review the literature for studies reporting on the use of SIA, with or without RED. METHODS: A systematic review according to the PRISMA guidelines was performed. Quantitative synthesis was applied when possible. RESULTS: 87 studies and 4665 patients (5161 lesions) were included (63.9% male). 46.7% of patients had critical limb ischemia at the time of the intervention. Two RED types were used (Pioneer and Outback). Sixty-eight studies included lesions treated with SIA without RED, 17 studies included lesions treated with RED only, and two studies included a comparison between the two treatment methods. In total, 3898 (83.6%) patients were treated with SIA without RED and 754 (12.2%) with RED. Procedural success rate ranged from 64.5%-100% (92.5% for SIA without RED, 88.3% for RED cases). The complication rate ranged from 1.6% - 28% among different studies (cumulative rates: SIA: 9.1%, RED 9.3%). Perforations occurred in 1.6% of the total population (n = 46). Primary patency at one year ranged from 22% to 94.1%. Newer studies had a higher patency rate, ranging from 70% to 94.1%. CONCLUSION: SIA with or without RED is a valuable alternative to intraluminal crossing for endovascular treatment of FP CTOs. Procedural success was excellent for both techniques, while the cumulative complication rate was numerically lower in the RED group. Short- and long-term outcomes were acceptable for both techniques.

Laparoscopic Sleeve Gastrectomy Carries a Lower Perioperative Mortality Including Sudden Cardiac Death over Roux-en-Y Gastric Bypass in Patients with a Prior Cardiac History: An MBSAQIP Analysis.

BACKGROUND: Although bariatric surgery has proven beneficial for those with cardiovascular disease (CVD), the overall and procedure-specific risk associated with bariatric surgery in this patient population remains unknown. DESIGN: Patients who underwent primary laparoscopic, laparoscopic-assisted, or robotic-assisted Roux-En-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) at a MBSAQIP-accredited center were included (n = 494,611). Exposures include history of MI, PCI, or cardiac surgery who underwent RYGB or SG. Outcome measures were 30-day mortality, perioperative cardiac arrest, and rehospitalization. RESULTS: Of 494,611 patients enrolled in MBSAQIP, 15,923 had a history of MI, PCI, or cardiac surgery (prior cardiac history). Patient history of MI, PCI, and cardiac surgery was associated with significantly increased adjusted risk of perioperative cardiac arrest requiring CPR (OR: 2.31, 2.12, 2.42, respectively) and adjusted 30-day mortality (OR: 1.72, 1.50, 1.68, respectively). Prior cardiac history was associated with increased adjusted 30-day readmission rate (MI - OR, 1.42; PCI - OR, 1.45; and cardiac surgery - OR, 1.68). Further, 30-day postoperative readmission, postoperative cardiac arrest, and death were lower for patients undergoing SG compared to RYGB (OR: 0.48, 0.49, and 0.54 respectively). CONCLUSION AND RELEVANCE: Prior cardiac history was associated with significant greater risk of perioperative cardiac arrest and 30-day mortality among patients undergoing bariatric surgery. SG was associated with less adverse events than RYGB among this population. While there is a clear benefit to weight loss in patients with CVD, it is important to consider whether cardiac patients considering bariatric surgery may require additional preoperative optimization, perioperative interventions, and postoperative monitoring.

Diagnosis, Treatment and Follow Up of Acute Pulmonary Embolism: Consensus Practice from the PERT Consortium.

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.

Transfemoral Valve-in-Valve Sapien 3 in a Patient with an Ascending Aortic Aneurysm.

The presence of thoracic aortic aneurysms, particularly in the ascending aorta and arch, presents a challenge to transcatheter aortic valve replacement. We present a case of TAVR in the presence of a chronic ascending aortic aneurysm. doi: 10.1111/jocs.12724 (J Card Surg 2016;31:318-320).

Statins and cognitive function: an updated review.

Ischemic heart disease remains the leading cause of death in the USA. Statins have substantially contributed to the decline in mortality due to heart disease. Historically, statins are hypothesized to be neuroprotective and beneficial in dementia, but recent reports have suggested an association with transient cognitive decline. We have critically appraised the relationship between statins and cognitive function in this review. Most of the data are observational and reported a protective effect of statins on dementia and Alzheimer's disease in patients with normal cognition at baseline. Few studies, including two randomized control trials, were unable to find a statistically significant decrease in the risk or improvement in patients with established dementia or decline in cognitive function with statin use. As more randomized control trials are required to definitively settle this, cardiovascular benefits of statins must be weighed against the risks of cognitive decline on an individual basis.