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Literature Review on Improving Cardiovascular Health With Statins

Info: 5720 words (23 pages) Nursing Literature Review
Published: 19th Apr 2021

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Tagged: cardiovascular diseasePICOT

Introduction

The increasing levels of acuity in current healthcare delivery requires continuous research to unearth the best evidence in improving patients care. Nurses have a central role in evidence-based practice as they tend to be key drivers of the various findings that result from various research. As researches continue to find better ways of improving cardiovascular health using statins and other medications, it has become important to know how to use statins effectively to reduce the risk for cardiovascular disease in patients with history of cardiovascular diseases.

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  This paper aims at examining how treating patients with no history of cardiovascular disease or heart disease with statins can help reduce complications or death. Statins happen to be the first line of medication used to treat patients with high cholesterol. This paper will critically look at the efficacy of statins when prescribed at the 7.5% threshold rather than the usual 20% threshold over ten years among patients with no cardiovascular disease risk.

Problem

In the United States and around the world, significant number of people die from cardiovascular diseases annually. This has led to measures to help curtail this problem and look for lasting solutions especially among those with no risk. According to the CDC, Heart disease happens to be the leading cause of death in the United States. More than 600,000 Americans die of heart disease each year which is one in every four deaths (Center for Disease Prevention and Control, 2018). The world health organization estimates that Cardiovascular diseases or heart diseases accounts for thirty-one percent of deaths globally. This is 17.9 million deaths every single year.

The United States Preventive Services Task Force is an independent body which came out in 2016 to recommend that adults without a history of cardiovascular disease take a low- to moderate-dose statin to help prevent cardiovascular events as well as mortality if they meet these three criteria. The criteria includes aged 40 to 75 years; have one or more cardiovascular disease risk factors like smoking, hypertension, diabetes, and dyslipidemia; and a calculated 10-year risk of a cardiovascular event of 10% or greater (USPSTF, 2018).

PICOT Question

 Among adults with no history of Cardiovascular disease how does prescribing Statins at the 7.5% threshold compared to the 20% threshold decrease the risk of Cardiovascular disease within ten years? (P-Adults with no history of cardiovascular disease, I- Prescribing statins at the 7.5% threshold, C- Prescribing statins at the 20% threshold, O- Decrease the risk of cardiovascular disease, T- Ten years).

Conceptual Definitions

The National Heart, Lung, and Blood Institute defines cardiovascular disease or heart disease or Coronary heart disease as diseases of the blood vessel of the heart which can lead to a heart attack. A heart attack happens when an artery becomes blocked, preventing oxygen and nutrients from getting to the heart (NIH, 2018). There are risk factors to developing heart disease; some of the risk factors include family history, high cholesterol, high blood pressure, smoking, family history, and inactivity.

Also, heart disease is often diagnosed based on a patient’s family and medical history, physical assessment, laboratory tests and procedures, and the patient’s risk factors. There is no single test used to diagnose heart disease. Blood tests are usually used to test for high cholesterol levels, blood sugar levels, and proteins produced by the heart muscle. Laboratory tests and procedures like an EKG or Electrocardiogram is used to record the electrical activity of the heart. An echo or Echocardiography helps determine the shape and size of the heart and how the heart is pumping or working utilizing sound waves. A chest x-ray can also be used to examine the heart. A cardiac MRI or magnetic resonance imaging is used to measure blood flow in the heart. Other tests include stress test, cardiac catheterization, and coronary angiography. Treatment for heart disease typically includes medications like statins, cardiac rehabilitation, surgical procedures, and lifestyle changes.

Search Methods

 The PubMed database with MeSH as well the One search feature on the Cedarville University’s website was used to search for articles. Search criteria and keywords used during the search process is shown in flow diagram named as Figure 1.

MeSH and subject headings search for: Cardiovascular diseases AND Statins AND Prevention

Cochrane Systematic Reviews and Register of Controlled Trials: 624

CINAHL: 1087

Medline: 2161

PubMed: 7251

N=11,123

Filters applied

Date of publication (2008-2018), peer reviewed journals, English, humans, adult subjects, and US geography

Articles removed N=10,089

Irrelevant by title and/or abstracts:

N=999              

Excluded N=29:

-          Irrelevant after another review (17) - Expert Opinion (4)

-          Case study (5)   

-          Editorial (3)   

Unique Abstracts reviewed:

N=35

Added after reviewing references N=0

Studies Included:

N=6

Figure 1. Flow Diagram

Summary of the Evidence

 After rigorous searches, six articles were used. All six articles were level 1 which are the highest level of evidence. The first resource is a Systematic review with meta-analysis by Chou et al. (2016) with an objective to review the benefits and harms of statins for the prevention of Cardiovascular disease (CVD). This article found out that adults who have never had a past cardiovascular disease event but are at increased CVD risk, had reduced risk of all-cause and cardiovascular mortality and CVD events with statin therapy with greater absolute benefits in patients at greater baseline risk. The second evidence by Brugts et al. (2009) is a Meta-analysis of randomized trials that investigated if statins reduce all-cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors. The study also examined if the effects are similar in men and women, in young and older than 65 years, and in people with Diabetes Mellitus. Brugts et al. (2009) suggests that in patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events (Brugts et al., 2009).

 It is without a doubt that Statin therapy help improve the lives of patients with Cardiovascular Disease. However, its benefits in patients with low risk for cardiovascular events is what the meta-analysis by Mihaylova et al. (2012) explored. Mihaylova et al. (2012) concluded that in individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. The fourth article is similar to the first article as they both investigated the benefits and harms of statins in patients with no history of cardiovascular disease. Taylor et al. (2013) after looking at the effects of statins in patients with no history of cardiovascular disease arrived at the conclusion that total cholesterol and LDL cholesterol after statin use.

 The only article that evaluated the efficacy of statins primarily on the elderly population was by Teng et al. (2015), which focused on those older than 65 years. The authors recommended further studies to evaluate statins on fatal MI, stroke, and all-cause mortality after concluding that statins play a role in preventing cardiovascular diseases in the elderly population. Most of the articles about statin use and its benefits have mostly white people as study participants. This final article focused on ethnically diversed population with no risk for cardiovascular disease. Yusuf et al. (2016), found out from their randomized control trial that patients from ethnically diverse populations who were treated with 10 mg of Rosuvastatin daily, had a significantly decreased risk of cardiovascular disease. All six literatures reviewed suggests that statins are effective in reducing the risk of cardiovascular disease which is summarized in the table (Table 2)

Citation

Conceptual Framework

Sample/Setting

Major Variables Studied and
Their Definitions

Outcome
Measurement

Data
Analysis

Findings

Level of Evidence

Quality of Evidence:

Critical Worth to Practice

 

Chou, R., Dana, T., Blazina, I., Daeges, M., & Jeanne, T. L. (2016). Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the US preventive services task force. Jama, 316(19), 2008-2024. http://dx.doi.org/10.1001/jama.2015.15629.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

To systematically review benefits and harms of statins for development of recommendations on statin therapy for prevention of CVD in adults 40 years or older without prior cardiovascular events.  

Design: Systematic review with meta-analysis. using 19 RCTs.

Method: A research librarian searched the Cochrane Central Register of Controlled

Trials (from 1991), the Cochrane Database of Systematic

Reviews (from 2005), and Ovid MEDLINE (from 1946) to June 2016 for English language publications and reference lists. After the draft report was posted for public comment and peer reviewed.  The search was updated in June

2016 and 1 additional trial was added.

N=71,344

19 RCTs

Adults greater than 40 years without CVD events

Mean ages 51-66 years

Independent variable: Using statins

Dependent variables:

DV1: CVD-related morbidity or mortality

DV2: All-cause mortality

DV3: Adverse reactions defined as cancer, fatal cancer myalgias, elevated aminotransferase levels, rhabdomyolysis, myopathy, renal dysfunction, cognitive harms, diabetes.

USPSTF quality level assessment and validity tools

Dersimonian-Laird random effects model

Internal validity assessed using USPSTF methods

NNT

ARD

risk ratio,

I2 statistic, sensitivity stratified analyses

DV1: CV mortality (10 trial) RR 0.69, 95% CI (0.54-0.88), ARD -0.43%, NNT 233 

DV2:   all-cause mortality (15 RCT) RR 0.86 (0.80-0.93), ARD -0.40%, NNT 250

DV3: serious adverse events (7 RCT) RR 0.99, 95% CI (0.94-1.04)

Level I

Strengths:

Two independent reviewers

Large sample size

NNT included

Limitations:

No access to patient data

Only 6 trials rated good quality

Limited age group

Researchers excluded non-English studies

Brugts, J. J., Yetgin, T., Hoeks, S. E., Gotto, A. M., Shepherd, J., Westendorp, R. G., de Craen, A. J., Knopp, R. H., Nakamura, H., Ridker, P., van Domburg, R.,Deckers, J. W. (2009). The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trials. BMJ (Clinical research ed.), 338, b2376. doi:10.1136/bmj.b2376

To investigate whether statins reduce all-cause mortality and major coronary and cerebrovascular events in people without established cardiovascular disease but with cardiovascular risk factors, and whether these effects are similar in men and women, in young and older (>65 years) people, and in people with diabetes mellitus.

Design/ Setting:

Meta-analysis of randomized trials.

Sample:/Setting:

10 RCT

n= 70,388

statin vs. placebo

mean age 63 years

34% women

23% w/DM

>80% without CVD

12 studies excluded

Independent variables:

IV1: statin use.

Placebo is the control group

Dependent variables:

DV1: all-cause mortality (primary endpoint)

DV2: Major coronary events

DV3: Major cerebrovascular events

DV4: Cancer

Egger regression test

OR

CI

I2, Q statistics and odd ratio

In patients without established cardiovascular disease but with cardiovascular risk factors, statin use was associated with significantly improved survival and large reductions in the risk of major cardiovascular events.

DV1: OR: 0.88, 95% CI (0.81-0.96)

DV2: OR 0.70 95% CI (0.61-0.81)

DV3: OR 0.81 95% CI (0.71-0.93)

DV4: OR 0.97 95%CI (0.89-1.05)

 

I

 

 

Strengths:

Large sample size

Level I study

Results from study can be used in practice

Jadad scale is used to determine quality of the studies,

Limitations

No NNT

3 of the trials included participants with CVD

Dose and type of statin differed between trials

 

Mihaylova, B., Emberson, J., Blackwell, L., Keech, A., Simes, J., Barnes, E. H., . . . Baigent, C. (2012). The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomized trials. Lancet, 380(9841), 581-590. http://dx.doi.org/10.1016/S0140-6736(12)60367-5

FUNDING: British Heart Foundation; UK Medical Research Council; Cancer Research UK; European Community Biomed Programme; Australian National Health and Medical Research Council; National Heart Foundation, Australia.

 

To determine the effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease

Design: Meta-analysis

Method: Earlier studies referenced. Analyzed 27 RCT that met 3 criteria: at least one intervention to lower LDL, unconfounded with respect to intervention, at least 1000 participants for at least 2 years

Sample/Setting:

27 RCT

Sample size: 174,149

Participants were assigned to baseline categories of 5-year risk from 12/2009-6/2011

Independent variables

IV1: minimum of 2 years statin use

IV2: Intensity of statin use

Dependent variables

DV1: Major vascular events

DV2: Major coronary events

DV3: Stroke

DV4: Revascularization

DV5: Cancers

DV6: Cause-specific mortality

Cox proportional hazard models’ analysis tool

RR

CI

DV1: 0.79 RR

DV2: RR: 0.76

DV3: RR 0.85

DV4: RR 0.76

DV5: RR 1

DV6: RR 0.88

In individuals with 5-year risk of major vascular events lower than 10%, each 1 mmol/L reduction in LDL cholesterol produced an absolute reduction in major vascular events of about 11 per 1000 over 5 years. This benefit greatly exceeds any known hazards of statin therapy. Under present guidelines, such individuals would not typically be regarded as suitable for LDL-lowering statin therapy.

Level I

Strengths:

Studied benefit in primary prevention which is of clinical significance.

Inclusion of primary prevention trial data

Large sample size

Limitations:

More male than female

Participants

Search methods not described

Only data analysis tool

No NNT

Taylor, F., Huffman, T. F., Macedo, A. F., Moore, T., Burke, M., Smith, D. G., Ward, K., & Ebrahim, S.  (2013). Statins for the primary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews, 2013(1), Art. No.: CD004816. http://dx.doi.org/10.1002/14651858.CD004816.pub5

Funding and sponsorship from: Department of Health Funding for the Cochrane Heart Group,  UK..

 

Primary prevention of CVD

 

Design: systematic review with meta-analysis.

Method: 2 review authors searched and independently read RCT from Cochrane Register of Controlled Trials, Medline (1950-2011), and Embase (1980-2012).

18 RCT with both genders

Aged 18 and older

Less than 10% previous history of CVD from 1994-2008

Eliminated RCT testing statins for the treatment of other chronic illnesses

IV: minimum of 1-year statin use

DV1: All-cause mortality

DV2: Fatal and non-fatal CHD events

DV3: Fatal and non-fatal CVD events

DV4: Fatal and non-fatal stroke events

DV5: Combined fatal and non-fatal CHD, CVD, stroke

DV6: Revascularization

DV7: Cholesterol

DV8: Adverse events-cancer, T2D, HS

Cochrane Handbook of Systematic Reviews

NNT

RR

OR

CI

DV1: NNT 96, OR 0.86

DV2: NNT 56, RR 0.73

DV3: RR 0.75

DV4: RR 0.78

DV5: RR 0.65

DV6: RR 0.62

DV7: -1.05 (net difference)

DV8: RR 1

CI-95%

Level I

Strengths:

Comprehensive review of RCT

Level I study

2 independent review authors

Review of adverse effects

Limitations:

Not all trials reported adverse events

Some trials included people with CVD

Some trials stopped early

Does not look at the risk thresholds but rather focuses on the harm

Teng, M. 1., Lin, L., Zhao, Y. J., Khoo, A. L, Davis, B. R., Yong, Q. W., Yeo, T. C., & Lim, B (2015). Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis. 32(8), http://dx.doi.org/10. 1007/s40266-015-0290-9

 

 

 

To critically evaluate the efficacy and safety of statins for primary prevention of cardiovascular disease (CVD) in the elderly.

 

Design: Systematic Review and Meta-Analysis

Method: Review of literature from 2009 to 2014 based on the guide from the Agency for Healthcare Research and Quality (AHRQ)

Data bases used: PubMed and Cochrane library

The Cochrane Collaboration’s sensitivity and precision-maximizing strategy was adopted

2 reviewers screened full-text articles for eligibility

Sample/setting:

8 RCT

n= 25,952

statin vs. placebo

participants had to be > 65 years old without CVD

mean age 72.7 years

mean follow-up was 3.5 years

2 trials not designed to capture statin effect in older adults

6 trial double blind

Exclusion criteria:  participants younger than 65 years of age were excluded if they did not report results stratified by age.

Independent variables:

IV1: statin vs. placebo

Dependent variables:

DV1: All-cause mortality DV2: Total MI (Non-fatal and fatal)

DV3: Stroke, fatal and non-fatal

DV4: Major adverse cardiovascular events

sensitivity analysis

PRISMA adherence reports the results of SR

Cochrane Risk of Bias Tool

Chi square test

p values

random effects model in STATA software

CI

RR

DV1: RR 0.96, 95 % CI 0.88–1.04)

DV2: Total MI RR, 0.74, 95% CI, (0.61–0.90)

Nonfatal MI, RR (0.75, 95% CI (0.59-0.94)

Fatal MI, RR 0.43, 95% CI (0.09–2.01),

DV3: RR 0.85, 95 % CI (0.68–1.06)

DV4: RR 0.82, 95 % CI (0.74–0.92)

p=0.002

I

Strengths:

Large sample size

Level I study

Findings from study consistent with prior published meta-analyses of statins for primary prevention

Limitations:

data from two trials was not designed specifically to capture statin effect in older subjects

Yusuf, S., Bosch, J., Dagenais, G., Zhu, J., Xavier, D., Liu, L.,…Lonn, E. (2016). Cholesterol lowering in intermediate-risk persons without cardiovascular disease. The New England Journal of Medicine, 374, 2021-2031. doi:10.1056/NEJMoa1600176

 

 

 

 

 

 

 

 

To determine the benefits of statin use within intermediate-risk, ethnically varied persons without cardiovascular disease.

 

Design: randomized, placebo-controlled trial

Method: A pragmatic, multicenter, long-term, international, double-blind, randomized, placebo-controlled trial

Sample/setting: 12,705 participants were randomly assigned, who did not have cardiovascular disease and were at intermediate risk to receive rosuvastatin at a dose of 10 mg per day or placebo.

228 centers in 21 countries.

Independent variables:

IV1= rosuvastatin 10mg dose

IV2= placebo

Dependent variables

DV1: Death from cardiovascular events

DV2: Non-fatal MI

DV3: Non-fatal stroke

DV4: Revascularization

DV5: Heart failure

DV6: Resuscitated cardiac arrest

Cox proportional hazards model

CI

P value

NNT

DV1: 0.89 (0.72-1.11), 95% CI

DV2: 0.65 (0.44-0.94), 95% CI

DV3: 0.70 (0.52-0.95), 95% CI

DV4: 0.68 (0.48-0.95), 95% CI

DV5: 0.72 (0.41-1.26), 95% CI

DV6: 0.99 (0.25-3.97), 95% CI

Composite of DV1-DV3: 0.76 (o.64-0.91), 95% CI, .0002 p-value, NNT 91

Composite of DV4-DV6: 0.75 (0.66-0.89). 95% CI, ,0.001 p-value, NNT 73

I

Strengths:

Large sample size N=12,705

Diversity of participants by gender, race, and ethnicity

NNT reported

Limitations:

initially entered a single-blind

High attrition rate

Critical Appraisal of the Evidence

 All six high level articles bodies of evidence can be used in answering the PICOT question posed earlier on. Also, the purpose of the studies, design and methods as well as study descriptions and their characteristics are clearly stated in most of the articles. In Mihaylova et al., (2012), a meta-analysis, the authors address a focused clinical question which focuses on the effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease. Search methods are not described but authors referred to earlier studies. The literature search included 27 randomized control trials with individual participant data from 22 trials of statin use versus control. There was a mean LDL cholesterol difference of 1·08 mmol/L; median follow-up 4·8 years, and five trials of more versus less statin. Participants were separated into five categories of baseline 5-year major vascular event risk on control therapy. The rate ratio (RR) per 1·0 mmol/L LDL cholesterol reduction was estimated. The Cox proportional hazard models’ analysis tool was used for measurement. Bias or conflict of interest is noted as most of the trials included were funded by pharmaceutical companies and some members of the writing team received cost reimbursement from pharmaceutical companies. Overall, this can be defended as a valid study. In terms of reliability, the intervention was precise because of the narrow confidence interval of 95% (Mihaylova et al., 2012)

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The article by Taylor et al (2013), assessed the harms and benefits of statins in people with no history of cardiovascular disease (CVD) by performing a comprehensive literature review. Although the setting was not stated in this study, two review authors read results from searches on electronic databases (see below) to identify relevant articles.  Full articles were retrieved for assessment and read independently by two review authors.  The databases used include Cochrane Central Register of Controlled Trials, Medline, and Embase. Also, the reviewers rated the quality of the studies reviewed by using the criteria described in Cochrane Handbook of Systematic Reviews which forced the reviewers to evaluate sequence generation, measures to conceal allocation, blinding, completeness of outcome data, and lack of selective reporting.  The evaluation method for each measure was described. Bias was not reported. Intervention was not precise because of the high NNT and wide confidence interval. Overall, this study is a well-conducted systematic review of many Randomized Control Trials. 

Another article that looked at the benefits and harms of statin for prevention of cardiovascular disease is by Chou et al, (2016), this study is reliable and valid. This systematic review and meta-analysis addressed five focused clinical questions- what are benefits of statins in reducing the incidence of CVD-related morbidity or mortality or all-cause mortality in asymptomatic adults 40 years or older without prior CVD event; what are the benefits of statin treatment to achieve target LDL-C levels vs other treatment strategies; Do the benefits vary in subgroups defined by demographic or clinical characteristics; what are the harms of statin treatment; and how do benefits and harms vary according to statin treatment potency? The databases researchers used include Cochran Database of Systematic reviews, Cochrane Central Register of Controlled Trials, and MEDLINE. The intervention in this study is precise with a 95% confidence interval and clinically significant.The other three articles are all meta-analysis and randomized control trial which are reliable and valid. In Brugts et al. (2016) researchers used Egger regression test to test for bias. Brugts et al. (2016), Yusuf et al. (2016), and Teng et al. (2015) are all valid and reliable studies.

Overall, the strengths and weaknesses of articles were stated in the studies to help readers make informed decisions. Study selections were made based on the strengths of the studies and how it answered the PICOT question. Some of the noted strengths in the article by Chou et al. (2016) include two independent reviewers; large sample size; and including NNT while weaknesses or limitations noted include no access to patient data, limited age group of participants, and researchers excluding non-English studies. Some strength of all the articles is the fact that they are all level 1 studies, and relevant to the PICOT question posed.

Conclusion

 All articles examined show that the statin use is effective in reducing the risk of cardiovascular events in patients with no risk. As high as one in four deaths in the United States is due to heart disease. This calls for measures to reduce mortality related to cardiovascular disease. Statins have always been the first medication prescribed to patients who are at increased risk. As noted in the article by Brugt et a. (2016), Statin therapy was associated with a significant risk reduction in all-cause mortality of 12%, in major coronary events of 30%, and in major cerebrovascular events of 19%. After careful review of all evidence, it is clear that statins are effective when prescribed at the 7.5% threshold rather than the usual 20% threshold over ten years among patients with no cardiovascular disease risk.

References:

  • Brugts, J. J., Yetgin, T., Hoeks, S. E., Gotto, A. M., Shepherd, J., Westendorp, R. G., de Craen, A. J., Knopp, R. H., Nakamura, H., Ridker, P., van Domburg, R., Deckers, J. W. (2009). The benefits of statins in people without established cardiovascular disease but with cardiovascular risk factors: meta-analysis of randomized controlled trials. BMJ (Clinical research ed.), 338, b2376. doi:10.1136/bmj.b2376.
  • Center for Disease Prevention and Control. Heart Disease Facts (2018). Retrieved from https://www.cdc.gov/heartdisease/facts.htm.
  • Chou, R., Dana, T., Blazina, I., Daeges, M., & Jeanne, T. L. (2016). Statins for prevention of cardiovascular disease in adults: Evidence report and systematic review for the US preventive services task force. Jama, 316(19), 2008-2024. http://dx.doi.org/10.1001/jama.2015.15629.
  • Mihaylova, B., Emberson, J., Blackwell, L., Keech, A., Simes, J., Barnes, E. H., Baigent, C. (2012). The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: Meta-analysis of individual data from 27 randomized trials. Lancet, 380(9841), 581-590. http://dx.doi.org/10.1016/S0140-6736 (12)60367-5
  • National Heart, Lung, and Blood Institute. Lower Heart Disease Risk (2018). Retrieved from https://www.nhlbi.nih.gov/health/educational/hearttruth/lower-risk/what-is-heart-disease.htm
  • Teng, M. 1., Lin, L., Zhao, Y. J., Khoo, A. L, Davis, B. R., Yong, Q. W., Yeo, T. C., & Lim, B.(2015). Statins for Primary Prevention of Cardiovascular Disease in Elderly Patients: Systematic Review and Meta-Analysis. 32(8), http://dx.doi.org/10. 1007/s40266-015-0290-9.
  • Taylor, F., Ward, K., Moore, T. H., Burke, M., Smith, G. D., Casas, J. P., & Ebrahim, S. (2011). Statins for the primary prevention of cardiovascular disease. The Cochrane Database of Systematic Reviews, (1), CD004816. Advance online publication. http://doi.org./10.1002/14651858.CD004816.
  • US Preventive Services Task Force. Final Recommendation Statement Statin Use for the Primary Prevention of Cardiovascular Disease in Adults: Preventive Medication (2018). Retrieved from..https://www.uspreventiveservicestaskforce.org/Page/Document/Recommendation
  • StatementFinal/statin-use-in-adults-preventive-medication1
  • World Health Organization. Cardiovascular Disease. (2018). Retrieved from https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

 

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