A study in high-risk, maximally pretreated patients to determine the potential use of PCSK9 inhibitors at various thresholds of total and LDL cholesterol levels

PURPOSE OF THE STUDY: Statins and ezetimibe reduce low-density lipoprotein cholesterol (LDL-c) and cardiovascular disease (CVD) risk. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower LDL-c by 50%-70% and might be useful in refractory patients. The National Institute for Health and Care Excellence (NICE) technology appraisal guidance (TAG) recommends use of these drugs in secondary prevention and familial hypercholesterolaemia (FH) at differing LDL-c thresholds. We have estimated the proportion of patients in whom this third-line drug might be useful. STUDY DESIGN: We used data from a lipid-lowering audit programme to study 72 with FH and/or CVD of 271 patients referred over 12 months who failed to achieve target total cholesterol (TC) and LDL-c levels. All 72 patients were treated with ezetimibe, and 69 cases also received statins. We used LDL-c thresholds 1.5-5.5 mmol/L to estimate how many of these refractory patients could benefit from PCSK9 inhibitors. RESULTS: In 72 patients, TC and LDL-c targets were not met by 64 and 53 patients, respectively. We judged using the NICE TAG that only one patient (1.4% ezetimibe requiring and 0.4% total referrals) required a PCSK9 inhibitor. CONCLUSIONS: We determined that the proportion of patients eligible for a PCSK9 inhibitor at various TC and LDL-c levels is modest. This may reflect the use of all available statins in UK lipid clinics often at non-daily frequency. We suggest that cost-effective use of PCSK9 inhibitors requires prescribing being restricted to clinicians working in specialised lipid clinics

Marginal role for 53 common genetic variants in cardiovascular disease prediction.

OBJECTIVE: We investigated discrimination and calibration of cardiovascular disease (CVD) risk scores when genotypic was added to phenotypic information. The potential of genetic information for those at intermediate risk by a phenotype-based risk score was assessed. METHODS: Data were from seven prospective studies including 11 851 individuals initially free of CVD or diabetes, with 1444 incident CVD events over 10 years' follow-up. We calculated a score from 53 CVD-related single nucleotide polymorphisms and an established CVD risk equation 'QRISK-2' comprising phenotypic measures. The area under the receiver operating characteristic curve (AUROC), detection rate for given false-positive rate (FPR) and net reclassification improvement (NRI) index were estimated for gene scores alone and in addition to the QRISK-2 CVD risk score. We also evaluated use of genetic information only for those at intermediate risk according to QRISK-2. RESULTS: The AUROC was 0.635 for QRISK-2 alone and 0.623 with addition of the gene score. The detection rate for 5% FPR improved from 11.9% to 12.0% when the gene score was added. For a 10-year CVD risk cut-off point of 10%, the NRI was 0.25% when the gene score was added to QRISK-2. Applying the genetic risk score only to those with QRISK-2 risk of 10%-<20% and prescribing statins where risk exceeded 20% suggested that genetic information could prevent one additional event for every 462 people screened. CONCLUSION: The gene score produced minimal incremental population-wide utility over phenotypic risk prediction of CVD. Tailored prediction using genetic information for those at intermediate risk may have clinical utility

Lifestyle advice and interventions for cardiovascular risk reduction: A systematic review of guidelines.

BACKGROUND: Lifestyle factors are important in preventing cardiovascular disease (CVD) development. We aimed to systematically review guidelines on primary prevention of CVD and their recommendations on lifestyle advice or intervention, in order to guide primary prevention programs. METHODS: Publications in MEDLINE, CINAHL over 7 years since May 3, 2009 were identified. G-I-N International Guideline Library, National Guidelines Clearinghouse, National Library for Health Guideline finder, Canadian Medical Association InfoBase were searched. On the February 8, 2017, we updated the search from Websites of organizations responsible for guidelines development. STUDY SELECTION: 2 reviewers screened the titles and abstracts to identify Guidelines from Western countries containing recommendations for lifestyle advice and interventions in primary prevention of CVD. DATA EXTRACTION: 2 reviewers independently assessed rigor of guideline development using the AGREEII instrument, and one extracted recommendations. RESULTS: Of the 7 guidelines identified, 6 showed good rigor of development (range 45-86%). The guidelines were consistent in recommendations for smoking cessation, limiting saturated fat and salt intake, avoiding transaturated-fat and sugar, with particular emphasis on sugar-sweetened beverages. Guidelines generally agreed on recommendations for physical activity levels and diets rich in fruit, vegetables, fish and wholegrains. Guidelines differed on recommendations for specific dietary patterns and alcohol consumption. Recommendations on psychological factors and sleep are currently limited. CONCLUSIONS: Current guidelines agree on the importance of lifestyle in the prevention of CVD with consensus on most factors including physical activity, smoking cessation and diet, which should be actively integrated in cardiovascular risk reduction programs aiming to improve clinical outcomes.Barts Charity for the HAPPY (Heart Attack Prevention Programme for You) London study (grant number 437/1412)

A qualitative study of cardiovascular disease risk communication in NHS Health Check using different risk calculators: protocol for the RIsk COmmunication in NHS Health Check (RICO) study. BMC family practice, 20(1), 11.

Background NHS Health Check is a national cardiovascular disease (CVD) risk assessment programme for 40–74 year olds in England, in which practitioners should assess and communicate CVD risk, supported by appropriate risk-management advice and goal-setting. This requires effective communication, to equip patients with knowledge and intention to act. Currently, the QRISK®2 10-year CVD risk score is most common way in which CVD risk is estimated. Newer tools, such as JBS3, allow manipulation of risk factors and can demonstrate the impact of positive actions. However, the use, and relative value, of these tools within CVD risk communication is unknown. We will explore practitioner and patient CVD risk perceptions when using QRISK®2 or JBS3, the associated advice or treatment offered by the practitioner, and patients’ responses. Methods RIsk COmmunication in NHS Health Check (RICO) is a qualitative study with quantitative process evaluation. Twelve general practices in the West Midlands of England will be randomised to one of two groups: usual practice, in which practitioners use QRISK®2 to assess and communicate CVD risk; intervention, in which practitioners use JBS3. Twenty Health Checks per practice will be video-recorded (n = 240, 120 per group), with patients stratified by age, gender and ethnicity. Post-Health Check, video-stimulated recall (VSR) interviews will be conducted with 48 patients (n = 24 per group) and all practitioners (n = 12–18), using video excerpts to enhance participant recall/reflection. Patient medical record reviews will detect health-protective actions in the first 12-weeks following a Health Check (e.g., lifestyle referrals, statin prescription). Risk communication, patient response and intentions for health-protective behaviours in each group will be explored through thematic analysis of video-recorded Health Checks (using Protection Motivation Theory as a framework) and VSR interviews. Process evaluation will include between-group comparisons of quantitatively coded Health Check content and post-Health Check patient outcomes. Finally, 10 patients with the most positive intentions or behaviours will be selected for case study analysis (using all data sources). Discussion This study will produce novel insights about the utility of QRISK®2 and JBS3 to promote patient and practitioner understanding and perception of CVD risk and associated implications for patient intentions with respect to health-protective behaviours (and underlying mechanisms). Recommendations for practice will be developed

Enhanced invitation methods and uptake of health checks in primary care. Rapid randomised controlled trial using electronic health records

Background: A national programme of health checks to identify risk of cardiovascular disease is being rolled out but is encountering difficulties of low uptake. Objective: To evaluate the effectiveness of an enhanced invitation method using the Question-Behaviour Effect (QBE), with or without the offer of a financial incentive to return the QBE questionnaire, at increasing the uptake of health checks. Secondary objectives were to evaluate reasons for low uptake of invitations and to compare case-mix for invited and opportunistic health checks. Trial design: Three-arm randomised trial. Participants: All participants invited for health checks from 18 general practices. Randomisation: Individual participants were randomised. Interventions: i) standard health check invitation only, ii) QBE questionnaire followed by standard invitation; iii) QBE questionnaire with offer of a financial incentive to return the questionnaire, followed by standard invitation. Outcomes: The primary outcome was completion of health check within six months of randomisation. A P value of 0.0167 was used for significance. Case-mix was evaluated for invited and opportunistic health checks. Blinding: Participants were not aware that several types of invitation were in use. The research team were blind to trial arm allocation at outcome data extraction. Results: There were 12,459 participants allocated and health check uptake was evaluated for 12,052 participants for whom outcome data were collected. Health check uptake was: standard invitation, 590 / 4,095 (14.4%); QBE questionnaire, 630 / 3,988 (15.8%); QBE questionnaire and financial incentive, 629 / 3,969 (15.9%). The increase in uptake associated with QBE questionnaire was 1.43% (95% confidence interval -0.12 to 2.97%, P=0.070) and for the QBE questionnaire and offer of financial incentive was 1.52% (-0.03 to 3.07%, P=0.054). The difference in uptake associated with the offer of an incentive to return the QBE questionnaire was -0.01% (-1.59 to 1.58%, P=0.995). During the study, 58% of health check cardiovascular risk assessments did not follow a trial invitation. People who received ‘opportunistic’ health checks had greater odds of ≥10% cardiovascular disease (CVD) risk; adjusted odds ratio 1.70, 95% confidence interval 1.45 to 1.99, P<0.001) compared with invited health checks. Conclusion: Uptake of health checks following an invitation letter is low and is not increased through an enhanced invitation method using the QBE, with or without an incentive. A high proportion of all health checks are performed opportunistically. Participants receiving opportunistic checks are at higher risk of CVD than those responding to standard invitations. Trial registration: Current Controlled Trials ISRCTN42856343