LDL-C-lowering therapies reduce major vascular events in patients aged ≥75 y.

SOURCE CITATION: Gencer B, Marston NA, Im K, et al. Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials. Lancet. 2020;396:1637-43. 33186535.

Cataracts and statins. A disproportionality analysis using data from VigiBase.

The basis of the association between statin use and cataract has been explored using the World Health Organization (WHO) global database of individual case safety reports (ICSRs) for drug monitoring (VigiBase) through January 2019. The reporting odds ratios (RORs) as a measure of disproportionality for reported cataracts and individual statins have been calculated. Subgroup analyses according statin lipophilicity, sex, and age groups have been performed. Moreover, RORs have been calculated for non-statin lipid lowering drugs. An increased disproportionality have been found for most individual statins lovastatin: [ROR: 14.80, 95% confidence interval (CI): 13.30, 16.46)], atorvastatin (ROR: 3.48, 95% CI 3.19-3.80), pravastatin (ROR: 3.15, 95% CI: 2.54-3.90), rosuvastatin (ROR: 2.90, 95% CI: 2.53-3.31), simvastatin (ROR: 2.27, 95%CI: 1.99-2.60), fluvastatin (ROR: 2.03, 95% CI: 1.33-3.08) and statins (overall) ROR: 3.66, 95% CI:3.46-3.86). Increased disproportionality for cataract and statins (drug-class) have been found regardless of statin lipophilicity, sex and group age (more or less than 65 years old). No disproportionality was found for other lipid-lowering drugs (ezetimibe, fibrates or PCSK9 inhibitors). These findings suggest an increased risk of cataract associated with statins as a drug-class. Further studies to characterize the risk are advised. Benefits and potential harms should be considered before starting treatment with statins.

Plasma oxysterol level in patients with coronary artery stenosis and its changes in response to the treatment with atorvastatin.

BACKGROUND: Considering the increasing incidence of coronary artery stenosis and its related complications, the importance of its etiology and inconsistent reports we aimed to determine the relationship between oxysterol, serum levels and severity of coronary atherosclerosis and effect of statins onoxysterol. METHODS: A total of 85 patients referred to Taleghani Hospital, Tehran, Iran during 2011-2012 withcoronary artery stenosis more than 75%, as determined by angiography, participated in the currentstudy. Their demographic information and history of smoking and taking atorvastatin was carefullyrecorded. Two milliliters of venous blood was obtained from each patient. The serum oxysterol levelof samples was measured using the enzyme-linked immunosorbent assay (ELISA) method. Statisticalanalysis was performed using SPSS v.19. RESULTS: Eighty five patients completed the study. Mean age of patients was 64.4 years; 51 (60%)were male; 55 (68%) had acute coronary syndrome and 30 (32%) had chronic stable angina.Mean±SD of plasma level of oxysterol was 24.8±0.2 pmol/ml. The normal range of oxysterol levelwas 13pmol/ml. Mean±SD of plasma oxysterol level in patients under statin therapy was 24.4±2.1pmol/ml. In patients without receiving statins, plasma oxysterol level was 26.38±1.6pmol/ml. CONCLUSION: Findings of the present study indicated significant correlation between serum oxysteroland severity of coronary artery stenosis. It also demonstrated that receiving atorvastatin is associatedwith significant reduction of plasma oxysterol level.

Development of reusable logic for determination of statin exposure-time from electronic health records.

OBJECTIVE: We aim to quantify HMG-CoA reductase inhibitor (statin) prescriber-intended exposure-time using a generalizable algorithm that interrogates data stored in the electronic health record (EHR). MATERIALS AND METHODS: This study was conducted using the Marshfield Clinic (MC) Personalized Medicine Research Project (PMRP) a central Wisconsin-based population and biobank with, on average, 30 years of electronic health data available in the independently-developed MC Cattails MD EHR. Individuals with evidence of statin exposure were identified from the electronic records, and manual chart abstraction of all mentions of prescribed statins was completed. We then performed electronic chart abstraction of prescriber-intended exposure time for statins, using previously identified logic to capture pill-splitting events, normalizing dosages to atorvastatin-equivalent dose. Four models using iterative training sets were tested to capture statin end-dates. Calculated cumulative provider-intended exposures were compared to manually abstracted gold-standard measures of ordered statin prescriptions, and aggregate model results (totals) for training and validation populations were compared. The most successful model was the one with the smallest discordance between modeled and manually abstracted Atorvastatin 10mg/year Equivalents (AEs). RESULTS: Of the approximately 20,000 patients enrolled in the PMRP, 6243 were identified with statin exposure during the study period (1997-2011), 59.8% of whom had been prescribed multiple statins over an average of approximately 11 years. When the best-fit algorithm was implemented and validated by manual chart review for the statin-ordered population, it was found to capture 95.9% of the correlation between calculated and expected statin provider-intended exposure time for a random validation set, and the best-fit model was able to predict intended statin exposure to within a standard deviation of 2.6 AEs, with a standard error of +0.23 AEs. CONCLUSION: We demonstrate that normalized provider-intended statin exposure time can be estimated using a combination of structured clinical data sources, including a medications ordering system and a clinical appointment coordination system, supplemented with text data from clinical notes.

Monitoring and treatment of hypercholesterolemia after an atherosclerotic cardiovascular disease event in Denmark from 2015 to 2020.

BACKGROUND AND AIMS: Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event. METHODS: Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured. RESULTS: A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated. CONCLUSIONS: Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.

Proactive multifactorial intervention strategy reduces the risk of cardiovascular disease estimated with region-specific risk assessment models in Pacific Asian patients participating in the CRUCIAL trial.

Despite race, ethnic, and regional differences in cardiovascular disease risk, many worldwide hypertension management guidelines recommend the use of the Framingham coronary heart disease (CHD) risk equation to guide treatment decisions. This subanalysis of the recently published CRUCIAL trial compared the treatment-related reductions in calculated CHD and stroke risk among Pacific Asian (PA) patients using a variety of region-specific risk assessment models. As a result, greater reductions in systolic and diastolic blood pressure, low-density lipoprotein cholesterol, and triglycerides were observed in the proactive multifactorial intervention (PMI) arm compared with the usual care arm at Week 52 for PA patients. The relative percentage change in 10-yr CHD risk between baseline and Week 52 in the PMI versus usual care arms was greatest using the NIPPON DATA80 fatal CHD model (LS [least square] mean difference -42.6%), and similar in the SCORE fatal CHD and Framingham total CHD models (LS mean difference -29.4% and -30.8%, respectively). The single-pill based PMI approach is consistently effective in reducing cardiovascular disease risk, evaluated using a variety of risk assessment models. (ClinicalTrials.gov registration number: NCT00407537).

Sex differences in LDL-C control in a primary care population: The PORTRAIT-DYS study.

BACKGROUND AND AIMS: Cardiovascular (CV) diseases show clear differences in clinical manifestation and treatment outcomes between men and women. To reduce sex disparities in achieving lipid-lowering therapy (LLT) goals, a sex-focused assessment is essential and more studies are needed to bring new evidence to clinicians. This study aims to assess the role of sex in attaining low-density lipoprotein cholesterol (LDL-C) goals, after correction for age, CV risk category, LLT intensity, and presence of mental health disorder and social deprivation. METHODS: A retrospective cohort analysis of patients aged 40-85, followed in 1 hospital and 14 primary care centers in Portugal, using electronic health records from 1/1/2012 to 31/12/2020, was performed. The analysis considered an episode-based design, where exposure consists of any time when LLT was started or intensity changed. The likelihood of reaching the LDL-C goal according to contemporary ESC/EAS guidelines was modeled using multivariate Cox regression. LDL-C goal achievement at 180 days was defined as the outcome. The analysis was repeated at 30-day follow-up intervals up to 360 days, and also stratified by CV risk category. RESULTS: We identified 40,032 exposure episodes (LLT initiation or intensity change) in 30,323 distinct patients. Male sex, older age, lower CV risk and increasing LLT intensity were associated with improved LDL-C control. Women were 22% less likely to reach the LDL-C goal than men (HR = 0.78, 95% CI:0.73, 0.82) independently of covariates. CONCLUSIONS: Women have a lower likelihood of attaining LDL-C goals than men after adjustment for LLT intensity, age, CV risk category, presence of mental health disorder and social deprivation. This finding underscores the need for further investigation and tailoring of LLT management strategies in women.

Prevalence of Statin Use and Predictors of Statin Initiation Among Patients with Alcohol-Related Cirrhosis - A Danish Nationwide Cohort Study.

Purpose: Statins reportedly increase the survival of patients with cirrhosis due to alcohol-related liver disease (ALD cirrhosis), but this association might be confounded by socioeconomic status. We examined the prevalence of statin use and socioeconomic and demographic predictors of statin initiation and discontinuation among patients with ALD cirrhosis. Patients and Methods: Using Danish nationwide healthcare registries, we examined statin use among patients diagnosed with ALD cirrhosis in 1997-2018. We computed the prevalence of statin use and incidence of statin initiation and discontinuation, and we used multivariable Cox regression to identify predictors of statin initiation and discontinuation. Results: We identified 28,260 patients with ALD cirrhosis in 1997-2018. During this period, the prevalence of statin use rose sharply, reaching 19.0% in late 2018. Among patients diagnosed with ALD cirrhosis after 2010, 16.9% were using statins when they were diagnosed with cirrhosis. Among the patients who did not use statins initially, those with lower educational attainment were more likely to begin taking them than those with higher attainment. Also, cohabiting patients were more likely to begin than patients who lived alone, and employed patients were more likely to begin compared to patients outside the labour force. Among current statin users, unemployment predicted statin discontinuation. Conclusion: The use of statins has become increasingly prevalent among Danish patients with ALD cirrhosis, reaching 19.0% in 2018. Employment, cohabitation, and a short education predicted statin initiation after ALD cirrhosis diagnosis, and unemployment predicted statin discontinuation. Overall, statin use was not a marker of a high socioeconomic status.

Cholesterol: An important actor on the cancer immune scene.

Based on the structural and signaling roles of cholesterol, which are necessary for immune cell activity, high concentrations of cholesterol and its metabolites not only trigger malignant cell activities but also impede immune responses against cancer cells. To proliferate and evade immune responses, tumor cells overcome environmental restrictions by changing their metabolic and signaling pathways. Overexpression of mevalonate pathway enzymes and low-density lipoprotein receptor cause elevated cholesterol synthesis and uptake, respectively. Accordingly, cholesterol can be considered as both a cause and an effect of cancer. Variations in the effects of blood cholesterol levels on the outcome of different types of cancer may depend on the stage of cancer. However, positive effects of cholesterol-lowering drugs have been reported in the treatment of patients with some malignancies.

Effect of the acute and chronic administration of Lupinus albus ß-conglutin on glycaemia, circulating cholesterol, and genes potentially involved.

Constituents of lupin seeds, like γ-conglutin and lupanine, have gained attention as potential complementary treatments for dysglycaemia management. Notwithstanding, the effect of other lupin components on carbohydrate metabolism, including ß-conglutin protein, has received little attention. Here, we investigated the influence of the acute and chronic administration of ß-conglutin on glycaemia modulation in normal and streptozotocin induced-to-diabetes rats. We analysed the liver transcriptome modulation exerted by ß-conglutin in diabetes-induced rats using DNA microarrays to scout for potential molecular targets and pathways involved in this biological response. The acute administration of ß-conglutin reduced the incremental area under the curve of glycaemia in normal and diabetes-induced animals. In a seven-day study with diabetic animals, glycaemia increased significantly in non-treated animals but remained unchanged in animals treated with a daily dose of ß-conglutin. Total cholesterol was significantly lower at the end of the experimental period (-21.8 %, p = 0.039). The microarray and gene ontology analyses revealed several targets and pathways potentially modulated by ß-conglutin treatment, including a possible down-regulation of Jun kinase activity. Moreover, our data indicate that targets related to oxidative stress, inflammation, and estrogenic activity might orchestrate these metabolic effects. In conclusion, our findings show that ß-conglutin may help manage postprandial glycaemia and reduce cholesterol levels under the dysglycaemia stage. We identified and proposed new potential molecular targets for further research related to the mechanism of action of ß-conglutin.

Effects of a Portfolio-Mediterranean Diet and a Mediterranean Diet with or without a Sterol-Enriched Yogurt in Individuals with Hypercholesterolemia.

BACKGROUND: A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone. METHODS: We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls. RESULTS: At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (P<0.001). CONCLUSION: A Portfolio-Mediterranean Diet, incorporating a new combination of functional foods such as oats or barley, plant sterols, chitosan, and green tea but not soy and nuts, may reduce LDL of 25% in the short term in individuals with hypercholesterolemia.

Ischemic Event Rates in Very-High-Risk Adults.

BACKGROUND: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline includes recommendations for intensive lipid-lowering therapy in patients at very high risk for atherosclerotic cardiovascular disease (ASCVD) events. OBJECTIVES: This study sought to estimate event rates among adults with a history of ASCVD who met and did not meet the definition of very high risk in the 2018 AHA/ACC cholesterol guideline. METHODS: Data from U.S. adults with health insurance in the MarketScan database who had a history of ASCVD on January 1, 2016 (n = 27,775) were analyzed. Very high risk for ASCVD events was defined as a history of ≥2 major ASCVD events or 1 event and ≥2 high-risk conditions. Patients were followed through December 31, 2017, for ASCVD events, including myocardial infarction, ischemic stroke, and major adverse limb events. RESULTS: Overall, 15,366 patients (55.3%) with ASCVD met the definition of very high risk. Among patients with and without very high risk, the ASCVD event rate per 1,000 person-years was 53.1 (95% confidence interval [CI]: 50.1 to 56.1) and 17.0 (95% CI: 15.2 to 18.9), respectively. Among patients with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions, the ASCVD event rate per 1,000 person-years was 89.8 (95% CI: 82.2 to 98.0) and 41.3 (95% CI: 38.3 to 44.4), respectively. The age- and sex-adjusted hazard ratios for ASCVD events among patients with very high risk, overall, with ≥2 major ASCVD events and with 1 event and ≥2 high-risk conditions versus those without very high risk were 2.98 (95% CI: 2.63 to 3.37), 4.89 (95% CI: 4.22 to 5.66), and 2.33 (95% CI: 2.04 to 2.66), respectively. CONCLUSIONS: The 2018 AHA/ACC cholesterol guideline directs intensive lipid-lowering therapy to adults with a very high ASCVD event rate.

Low Density Lipoprotein (LDL) Cholesterol as a Causal Role for Atherosclerotic Disease: Potential Role of PCSK9 Inhibitors.

Proprotein convertase subtilisin/kexin type 9 (PCSK9)-related discoveries of the turn of the century have translated into substantial novelty in dyslipidemia treatment in the last 5 years. With chronic preventable atherosclerotic cardiovascular diseases (ASCVD) representing an epidemic of morbidity and mortality worldwide, low-density lipoprotein cholesterol (LDL-c) reduction represents a public health priority. By overcoming two major statin-related issues, namely intolerance and ineffectiveness, PCSK9 inhibitors have offered a safe and effective option in selected clinical settings where LDL-c reduction is required. Herein, we recapitulate recent findings, clinical applications, and ASCVD prevention potential of PCSK9 inhibition, with focus on anti-PCSK9 monoclonal antibodies, evolocumab and alirocumab.

Evaluation of the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia in the secondary health care in the Brazilian Unified Health System (SUS)

Abstract Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. Dyslipidemia treatment can reduce the number of deaths caused by CVD, by decreasing the lipid profile. Evaluate the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia, regarding clinical and laboratory aspects. A quasi-experimental trial was performed in 12 months. The studied population was included patients with dyslipidemia who received a pharmacotherapeutic follow-up, which was evaluated according to the Pharmacotherapy Workup developed by the Brazilian Ministry of Health. Clinical and laboratory evaluations were performed at the baseline, after a 6 and 12-months period. The statistical analyzes were performed with the normality test of Lilliefors, Cramer Von Misses, and Anderson Darling, later the t-paired test. This study demonstrated that after 6-months of intervention, statistically significant results were verified in the reduction of LDL-cholesterol, total cholesterol, increase in HDL-cholesterol, and reduction in the blood pressure. It was observed that for high-risk patients, the achievement of targets in the lipid profile and HbA1C occurred only after 12-months, because, this population needs more aggressive targets and expressive interventions. Pharmacotherapeutic follow-up in patients with dyslipidemia reduced lipid blood levels and promoted positive clinical and laboratory outcomes.

Understanding deprescribing of preventive cardiovascular medication: a Q-methodology study in patients.

BACKGROUND: Patients with low cardiovascular disease (CVD) risk potentially use preventive cardiovascular medication unnecessarily. Our aim was to identify various viewpoints and beliefs concerning the preventive CVD management of patients with low CVD risk using preventive cardiovascular medication. Furthermore, we investigated whether certain viewpoints were related to a preference for deprescription or the continuation of preventive cardiovascular medication. METHODS: In 2015, we purposively sampled patients from the intervention arm of the Evaluating Cessation of STatins and Antihypertensive Treatment In primary Care (ECSTATIC) trial in the Netherlands for this study. Participants made Q-sorts by ranking 43 statements concerning preventive CVD management from "totally disagree" to "totally agree". These Q-sorts were analyzed using PQMethod 2.35 software. A varimax procedure presented the distinguishing viewpoints that were favored by our participants. We used group discussion quotations to underline our findings. For validation purposes, we asked participants how well each viewpoint fitted them. RESULTS: Of 291 invited patients, 33 participated. Thirty-one Q-sorts were analyzed. The following three viewpoints were found: 1) a controlling viewpoint, in which patients held the belief that monitoring blood pressure and cholesterol levels is important (n=13, of which seven had their medication deprescribed and six continued their medication); 2) an autonomous viewpoint, in which patients showed a dislike of medication (n=8, of which seven had their medication deprescribed and one had it continued); and 3) an afraid viewpoint, in which patients were fearful of developing CVD (n=8, of which two had their medication deprescribed and six had it continued). Seventy-four percent of the participants believed that the viewpoint to which they were assigned was a good fit. CONCLUSION: Three well-discriminating viewpoints about preventive CVD management were determined. Knowing and recognizing these viewpoints is effective for general practitioners when discussing the deprescribing of preventive cardiovascular medications with patients and may be used to promote implementation of deprescription.

Ezetimibe: Use, costs, and adverse events in Australia.

AIM: To analyze the subsidized use and reported adverse events of ezetimibe, used to lower cholesterol, in Australia over the 11 years following its inclusion on the Pharmaceutical Benefits Scheme (PBS) in 2004. METHODS: Pharmacoepidemiological analysis of dispensed prescriptions from Medicare Australia. Adverse event data were obtained from the Therapeutic Goods Administration. Use was measured by the defined daily dose (DDD) per 1000 population per day for each calendar year. Adverse events were counted by organ class system. RESULTS: Total ezetimibe use rose to 8.46 DDD/1000 population/d in the 11 years to 2015. Ezetimibe as a sole active ingredient was the most commonly dispensed formulation followed by the two combination products containing ezetimibe and 40 mg or 80 mg simvastatin. The average yearly increase in utilization was 19% with a 24% annual increase in costs to government (2006-2015) to $169.0 million in 2015. There were substantial differences in ezetimibe use between states, with no relationship to deaths from ischaemic heart disease (IHD) in each jurisdiction. The major reported adverse events were musculoskeletal and connective tissue disorders and gastrointestinal disorders. CONCLUSIONS: Ezetimibe use has increased rapidly in Australia since receiving public subsidy. Although the indications for subsidy are very restricted, there appears to have been widespread use, not explained by differential geographical IHD death rates. Latest guidelines still question the value of ezetimibe, so further discussion about whether the public spending on this medication for any potential improvement in population health outcomes is justified.

Early Effects of Intensive Lipid-Lowering Treatment on Plaque Characteristics Assessed by Virtual Histology Intravascular Ultrasound.

PURPOSE: The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome. MATERIALS AND METHODS: This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups. RESULTS: Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4±17.1 mg/dL vs. -36.8±17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group (-1.5±3.4 mm³ vs. 0.8±4.7 mm³, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R²=0.209). CONCLUSION: Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment.

Reduction in cardiovascular risk using a proactive multifactorial intervention is consistent among patients residing in Pacific Asian and non-Pacific Asian regions: a CRUCIAL trial subanalysis.

BACKGROUND: Few trials have compared different approaches to cardiovascular disease prevention among Pacific Asian (PA) populations. The Cluster Randomized Usual Care versus Caduet Investigation Assessing Long-term-risk (CRUCIAL) trial demonstrated that a proactive multifactorial intervention (PMI) approach (based on single-pill amlodipine/atorvastatin) resulted in a greater reduction in calculated Framingham 10-year coronary heart disease (CHD) risk compared with usual care (UC) among hypertensive patients with additional risk factors. One-third of CRUCIAL patients resided in the PA region. The aim of this subanalysis was to compare two approaches to cardiovascular risk factor management (PMI versus UC) among patients residing in PA and non-PA regions. METHODS: This subanalysis of the CRUCIAL trial compared treatment-related changes in calculated CHD risk among patients residing in PA and non-PA regions. Sensitivity analyses were conducted among men and women and those with and without diabetes. RESULTS: Overall, 448 patients (31.6%) resided in the PA region and 969 patients (68.4%) resided in non-PA regions. The PMI approach was more effective in reducing calculated CHD risk versus UC in both PA (-37.1% versus -3.5%; P<0.001) and non-PA regions (-31.1% versus -4.2%; P<0.001); region interaction P=0.131. PA patients had slightly greater reductions in total cholesterol compared with non-PA patients. PA patients without diabetes had slightly greater reductions in CHD risk compared with non-PA patients. Treatment effects were similar in men and women and those with diabetes. CONCLUSION: The PMI approach was more effective in reducing calculated Framingham 10-year CHD risk compared with UC among men and women with and without diabetes residing in the PA and non-PA region.