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Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials.
Koskinas, KC, Siontis, GCM, Piccolo, R, Mavridis, D, Räber, L, Mach, F, Windecker, S
European heart journal. 2018;(14):1172-1180
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Abstract
AIMS: Current evidence on dyslipidaemia management has expanded to novel treatments and very low achieved levels of low-density lipoprotein cholesterol (LDL-C). We sought to compare the clinical impact of more-intensive vs. less-intensive LDL-C lowering by means of statins and currently recommended non-statin medications in secondary prevention. METHODS AND RESULTS We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials of statins, ezetimibe, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, or bile acid sequestrants with >500 patients followed for ≥1 year. We employed random-effects models using risk ratios (RRs) with 95% confidence intervals (CIs) to compare outcomes. We included 19 trials (15 of statins, 3 of PCSK9 inhibitors, and 1 of ezetimibe) with 152 507 patients randomly assigned to more-intensive (n = 76 678) or less-intensive treatment (n = 75 829). More-intensive treatment was associated with 19% relative risk reduction for the primary outcome, major vascular events (MVEs; RR 0.81, 95% CI 0.77-0.86). Risk reduction was greater across higher baseline levels and greater achieved reductions of LDL-C. The clinical benefit was significant across varying types of more-intensive treatment and was consistent for statins (RR 0.81, 95% CI 0.76-0.86) and non-statin agents (PCSK9 inhibitors and ezetimibe; RR 0.85, 95% CI 0.77-0.94) as active (more-intensive) intervention (P-interaction = 0.38). Each 1.0 mmol/L reduction in LDL-C was associated with 19% relative decrease in MVE. Death, cardiovascular death, myocardial infarction, stroke, and coronary revascularization also favoured more-intensive treatment. CONCLUSION Reduction of MVE is proportional to the magnitude of LDL-C lowering across a broad spectrum of on-treatment levels in secondary prevention. Statin intensification and add-on treatment with PCSK9 inhibitors or ezetimibe are associated with significant reduction of cardiovascular morbidity in this very high-risk population.
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Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health: A Comprehensive Review.
Elagizi, A, Lavie, CJ, Marshall, K, DiNicolantonio, JJ, O'Keefe, JH, Milani, RV
Progress in cardiovascular diseases. 2018;(1):76-85
Abstract
The potential cardiovascular (CV) disease (CVD) benefits of Omega-3 Polyunsaturated Fatty Acids (OM3) have been intensely studied and debated for decades. Initial trials were performed in patients with low use of maximal medical therapy for CVD, and reported significant mortality benefits with the use of 1 g/day OM3 intervention following myocardial infarction (MI). More recent studies, including cohorts of patients receiving modern guideline directed medical therapy for CVD, have often not shown similar benefits with OM3 use. We conducted a literature review using PubMed, professional society guidelines, specific journal databases including New England Journal of Medicine and Journal of the American College of Cardiology from January 1, 2007 to December 31, 2017. References from selected articles were also reviewed, as well as key articles outside of the selected time-frame for their important findings or historical perspectives. Currently, there are no Class I recommendations from the American Heart Association (AHA) for the use of OM3, however, considering the safety of this therapy and beneficial findings of some modern studies (including patients with current maximal medical therapy for CVD), the AHA has recently expanded their list of Class II recommendations, in which treatment with OM3 for CVD benefit is reasonable. This review discusses the current state of the evidence, summarizes current professional recommendations, and provides recommendations for future research.
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Do PCSK9 inhibitors reduce cardiovascular events?
Kolber, MR, Nickonchuk, T, Turgeon, R
Canadian family physician Medecin de famille canadien. 2018;(9):669
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Long-term, telephone-based follow-up after stroke and TIA improves risk factors: 36-month results from the randomized controlled NAILED stroke risk factor trial.
Ögren, J, Irewall, AL, Söderström, L, Mooe, T
BMC neurology. 2018;(1):153
Abstract
BACKGROUND Strategies are needed to improve adherence to the blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) level recommendations after stroke and transient ischemic attack (TIA). We investigated whether nurse-led, telephone-based follow-up that included medication titration was more efficient than usual care in improving BP and LDL-C levels 36 months after discharge following stroke or TIA. METHODS All patients admitted for stroke or TIA at Östersund hospital that could participate in the telephone-based follow-up were considered eligible. Participants were randomized to either nurse-led, telephone-based follow-up (intervention) or usual care (control). BP and LDL-C were measured one month after discharge and yearly thereafter. Intervention group patients who did not meet the target values received additional follow-up, including lifestyle counselling and medication titration, to reach their treatment goals (BP < 140/90 mmHg, LDL-C < 2.5 mmol/L). The primary outcome was the systolic BP level 36 months after discharge. RESULTS Out of 871 randomized patients, 660 completed the 36-month follow-up. The mean systolic and diastolic BP values in the intervention group were 128.1 mmHg (95% CI 125.8-130.5) and 75.3 mmHg (95% CI 73.8-76.9), respectively. This was 6.1 mmHg (95% CI 3.6-8.6, p < 0.001) and 3.4 mmHg (95% CI 1.8-5.1, p < 0.001) lower than in the control group. The mean LDL-C level was 2.2 mmol/L in the intervention group, which was 0.3 mmol/L (95% CI 0.2-0.5, p < 0.001) lower than in controls. A larger proportion of the intervention group reached the treatment goal for BP (systolic: 79.4% vs. 55.3%, p < 0.001; diastolic: 90.3% vs. 77.9%, p < 0.001) as well as for LDL-C (69.3% vs. 48.9%, p < 0.001). CONCLUSIONS Compared with usual care, a nurse-led telephone-based intervention that included medication titration after stroke or TIA improved BP and LDL-C levels and increased the proportion of patients that reached the treatment target 36 months after discharge. TRIAL REGISTRATION ISRCTN Registry ISRCTN23868518 (retrospectively registered, June 19, 2012).
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Updates in the Metabolic Management of Calcium Stones.
Penniston, KL, Nakada, SY
Current urology reports. 2018;(6):41
Abstract
PURPOSE OF REVIEW Urinary risk factors, such as hypercalciuria, hypocitraturia, and hyperoxaluria, either in combination or alone, are associated with calcium stones. Dietary habits as well as underlying medical conditions can influence urinary risk factors. Evaluation of the conglomerate of patients' stone risks provides evidence for individualized medical management, an effective and patient-supported approach to prevention. RECENT FINDINGS Many patients with stones desire prevention to avoid repeated surgical interventions. Yet, recent practice pattern assessments and health care utilization data show that many patients are rarely referred for metabolic evaluation or management. Innovations in metabolic management over the past decade have improved its effectiveness in reducing risk and preventing calcium stones. Although no new pharmacologic agents for calcium stone prevention have recently become available, there is relatively new thinking about some diet-based approaches. This review will synthesize current evidence to support individualized metabolic management of calcium stones.
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Blood pressure-lowering drugs and secondary prevention of cardiovascular disease: systematic review and meta-analysis.
Xie, W, Zheng, F, Evangelou, E, Liu, O, Yang, Z, Chan, Q, Elliott, P, Wu, Y
Journal of hypertension. 2018;(6):1256-1265
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OBJECTIVE To systematically evaluate the efficacy of five commonly used blood pressure-lowering drugs in reducing cardiovascular events among patients with nonacute cardiovascular disease, but without heart failure. METHODS We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials on 18 March 2017. The primary outcome was fatal and nonfatal cardiovascular events, and the secondary outcomes were all-cause death, fatal and nonfatal myocardial infarction, and stroke. Pooled risk ratios and corresponding 95% confidence intervals (CIs) were calculated using Mantel-Haenszel random-effects meta-analyses. RESULTS Twenty-seven randomized controlled trials with 143 095 participants and a treatment duration of at least 12 months were included in our analyses. Fifteen trials enrolled patients with coronary artery disease, eight enrolled patients with cerebral artery disease, and four enrolled patients with cardiovascular disease. Of the 27 trials, 10 trials only included hypertensive patients. Compared with placebo, angiotensin-converting enzyme inhibitors (ACEIs) (risk ratio 0.85, 95% CI 0.78-0.92), angiotensin receptor blockers (risk ratio 0.92, 95% CI 0.87-0.98), and diuretics (risk ratio 0.77, 95% CI 0.66-0.90) significantly reduced the risk of cardiovascular events. Apart from this, ACEIs significantly reduced all secondary outcomes, calcium channel blockers, and diuretics reduced stroke significantly. No significant difference was found in head-to-head comparisons of each given drug class with any other class. CONCLUSIONS Although only ACEIs have evidences showing its effect in reducing cardiovascular events and all secondary outcomes, head-to-head comparisons did not provide strong evidence in difference in the effects between these blood pressure-lowering drugs.
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Lipid Testing and Statin Dosing After Acute Myocardial Infarction.
Wang, WT, Hellkamp, A, Doll, JA, Thomas, L, Navar, AM, Fonarow, GC, Julien, HM, Peterson, ED, Wang, TY
Journal of the American Heart Association. 2018;(3)
Abstract
BACKGROUND The 2013 American College of Cardiology/American Heart Association cholesterol guidelines recommend high-intensity statins for patients after myocardial infarction (MI) rather than treating to a low-density lipoprotein cholesterol goal, as the previous ATP III (Adult Treatment Panel third report) guidelines had advised. METHODS AND RESULTS To evaluate the frequency of postdischarge lipid testing and high-intensity statin use among MI patients discharged on a statin during the ATP III guidelines era, we linked ACTION (Acute Coronary Treatment and Intervention Outcomes Network) Registry data to Medicare claims for 11 046 MI patients aged ≥65 years who were discharged alive on a statin from 347 hospitals (2007-2009). Multivariable regression was used to evaluate the association between lipid testing and 1-year high-intensity statin use. Only 21% of MI patients were discharged on a high-intensity statin. By 90 days after MI, 44% of patients discharged on a statin underwent lipid testing (43% on low- or moderate-intensity statins and 49% on high-intensity statins; P=0.001). Follow-up lipid testing rates were 47% among patients with in-hospital low-density lipoprotein cholesterol ≥100 mg/dL and 47% among newly prescribed statin recipients. By 1 year, only 14% of patients were on high-intensity statins. Only 4% of patients discharged on low- or moderate-dose statin were uptitrated to high intensity; postdischarge lipid testing was associated with a slightly higher likelihood of high-intensity statin use by 1 year (5.4% versus 2.9%, adjusted odds ratio: 1.92; 95% confidence interval, 1.52-2.41). CONCLUSIONS Previous guidelines recommended low-density lipoprotein cholesterol goal-directed statin therapy, but lipid testing and high-intensity statin use were infrequent after MI. The American College of Cardiology/American Heart Association guidelines may promote more intensive cardiovascular risk reduction by eliminating treatment dependence on lipid testing.
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The secondary prevention of venous thromboembolism: Towards an individual therapeutic strategy.
Elmi, G, Pizzini, AM, Silingardi, M
Vascular. 2018;(6):670-682
Abstract
After the anticoagulant withdrawal, a substantial proportion of patients with venous thromboembolism will develop recurrent events. Whether to consider an extended treatment depends on the risk of recurrence and bleeding risk. The assessment of the individual risk profile remains a difficult task. Several basal and post-basal factors modulate the risk of recurrence and may help clinicians to select patients who can benefit from the extended therapy. During the year 2017, new evidence regarding the post-basal factors was provided by the Morgagni and Scope studies. Another interesting novelty was the VTE-BLEED score, the first bleeding risk score that obtained the external validation in venous thromboembolism setting. In secondary prevention, the use of direct oral anticoagulants is growing instead of vitamin K antagonist. Even at lower doses, direct oral anticoagulants showed to be effective and safe, to reduce all-cause mortality and seemed to be superior to placebo for the composite outcome of fatal bleeding and fatal recurrence. After the recently published Einstein-Choice trial, the role of aspirin has become truly marginal as rivaroxaban 10 mg showed a bleeding risk similar to aspirin 100 mg but a greater effectiveness reducing the relative risk of recurrence by about 70%. Another option for secondary prevention could be sulodexide, with a lower protective effect than direct oral anticoagulants but an interesting safety profile. In conclusion, in our opinion, an individual strategy taking into account the risk of recurrence, bleeding risk, therapeutic options and patient preferences is the most appropriate approach to secondary prevention of venous thromboembolism.
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Appropriateness of statin prescription in the elderly.
Ruscica, M, Macchi, C, Pavanello, C, Corsini, A, Sahebkar, A, Sirtori, CR
European journal of internal medicine. 2018;:33-40
Abstract
Statins, the most widely used drugs in the Western world, have become a pivotal component in the primary and secondary prevention of vascular diseases. Although benefits have been well documented in younger-than-75-year-old individuals, the value of statins in people aged >75years and over is controversial. The CTT meta-analysis calculated an absolute risk reduction of 0.6%/year per 38.7mg/dl reduction in LDL-C levels in patients aged >75years, that would translate into a number needed to treat of 167. However, the absolute effect of a 38.7mg/dl cholesterol lowering on the rate of annual ischemic heart disease mortality is 10-fold larger in older vs younger patients. In order to advise physician prescription, three major Guidelines have been published over the last few years, i.e. the AHA/ACC and the NLA in the US, and the ESC/EAS in Europe. Moreover, statin prescription in the elderly should also consider the cardiovascular outcomes of elderly patients reported in classical statin preventive trials which give important clues on adherence and persistence of use, as well as on drug safety. The present review discusses benefits of intensive vs moderate statin therapy, justifications for the use of aggressive lipid management in the very old and the use of statins in frail elderlies. The final decision on the therapeutic strategy with statins in elderlies at higher risk to develop cardiovascular events should be always based on a careful analysis of the patient's general health and on the presence of metabolic abnormalities or drug interactions potentially leading to risk.
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Interventions for improving modifiable risk factor control in the secondary prevention of stroke.
Bridgwood, B, Lager, KE, Mistri, AK, Khunti, K, Wilson, AD, Modi, P
The Cochrane database of systematic reviews. 2018;(5):CD009103
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BACKGROUND People with stroke or transient ischaemic attack (TIA) are at increased risk of future stroke and other cardiovascular events. Stroke services need to be configured to maximise the adoption of evidence-based strategies for secondary stroke prevention. Smoking-related interventions were examined in a separate review so were not considered in this review. This is an update of our 2014 review. OBJECTIVES To assess the effects of stroke service interventions for implementing secondary stroke prevention strategies on modifiable risk factor control, including patient adherence to prescribed medications, and the occurrence of secondary cardiovascular events. SEARCH METHODS We searched the Cochrane Stroke Group Trials Register (April 2017), the Cochrane Effective Practice and Organisation of Care Group Trials Register (April 2017), CENTRAL (the Cochrane Library 2017, issue 3), MEDLINE (1950 to April 2017), Embase (1981 to April 2017) and 10 additional databases including clinical trials registers. We located further studies by searching reference lists of articles and contacting authors of included studies. SELECTION CRITERIA We included randomised controlled trials (RCTs) that evaluated the effects of organisational or educational and behavioural interventions (compared with usual care) on modifiable risk factor control for secondary stroke prevention. DATA COLLECTION AND ANALYSIS Four review authors selected studies for inclusion and independently extracted data. The quality of the evidence as 'high', 'moderate', 'low' or 'very low' according to the GRADE approach (GRADEpro GDT).Three review authors assessed the risk of bias for the included studies. We sought missing data from trialists.The results are presented in 'Summary of findings' tables. MAIN RESULTS The updated review included 16 new studies involving 25,819 participants, resulting in a total of 42 studies including 33,840 participants. We used the Cochrane risk of bias tool and assessed three studies at high risk of bias; the remainder were considered to have a low risk of bias. We included 26 studies that predominantly evaluated organisational interventions and 16 that evaluated educational and behavioural interventions for participants. We pooled results where appropriate, although some clinical and methodological heterogeneity was present.Educational and behavioural interventions showed no clear differences on any of the review outcomes, which include mean systolic and diastolic blood pressure, mean body mass index, achievement of HbA1c target, lipid profile, mean HbA1c level, medication adherence, or recurrent cardiovascular events. There was moderate-quality evidence that organisational interventions resulted in improved blood pressure control, in particular an improvement in achieving target blood pressure (odds ratio (OR) 1.44, 95% confidence interval (CI) 1.09 to1.90; 13 studies; 23,631 participants). However, there were no significant changes in mean systolic blood pressure (mean difference (MD), -1.58 mmHg 95% CI -4.66 to 1.51; 16 studies; 17,490 participants) and mean diastolic blood pressure (MD -0.91 mmHg 95% CI -2.75 to 0.93; 14 studies; 17,178 participants). There were no significant changes in the remaining review outcomes. AUTHORS' CONCLUSIONS We found that organisational interventions may be associated with an improvement in achieving blood pressure target but we did not find any clear evidence that these interventions improve other modifiable risk factors (lipid profile, HbA1c, medication adherence) or reduce the incidence of recurrent cardiovascular events. Interventions, including patient education alone, did not lead to improvements in modifiable risk factor control or the prevention of recurrent cardiovascular events.