Statins

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Practice Change & CME

Mirvat Alasnag, MD

There are many scientific sessions happening around the globe that issue continuous medical education (CME) credits. Although the AHA Scientific Sessions 2018 covered a wide breadth of topics, I took particular interest in how the new Lipid Management Guidelines apply to women. My previous blog ended by citing a clinic encounter with a female patient. When I see how, as a woman cardiologist, I gained a newer perspective on hyperlipidemia, I realize these CME hours don’t capture the actual impact and changes in practice effected by presented data. Most busy clinicians don’t read every page of published guidelines. The lipid guidelines were summarized into ten key take home messages.

These points didn’t include women as a special population. I avail this opportunity to highlight two very different clinic visits: one before AHA Scientific Sessions 2018 & the second soon after it.

 

October 2018:

This is a 42-year-old female whose cardiovascular risk factors include poorly controlled Type II Diabetes, obesity and hypertension. She suffered an acute inferior myocardial infarction 3 months ago for which primary Percutaneous Intervention was performed with a second-generation drug eluting stent. She was on dual antiplatelet therapy, Lisinopril, Bisoprolol and Atorvastatin 40mg daily. She had not repeated any blood works since discharge (HbA1C 11.1 g/dL & LDL 162 mg/L). Her physical examination was unremarkable aside from weight gain (82 Kg to 85 Kg).

Me: Any chest pain or dyspnea?

She: No

Me: Why did your weight increase?

She: Shrug

Me: Ok I’ll get a dietician and educator to discuss this with you. You need to see your diabetologist. Continue DAPT. We need to drop your LDL, so I’d like to increase the dose of statin.

 

November 2018:

This is a 45-year-old female whose cardiovascular risk factors include Type II Diabetes, obesity and hypertension. She had a positive myocardial perfusion scan performed for angina. A coronary angiogram revealed non-obstructive coronary artery disease in January 2018. She was on aspirin, oral hypoglycemic agents, Bisoprolol and Atorvastatin 40mg daily. Her HbA1C 8 g/dL & LDL 118 mg/L. Her physical examination was unremarkable (weight 71 Kg).

Me: Any chest pain or dyspnea?

She: No, I’m feeling well.

Me: You’re only 45 years old. How many children do you have? Do you plan on having anymore?

She: Why? Will I have a heart attack if I do?

Me: I’m asking because of the statin. We need to discuss contraception if you aren’t planning anymore or alternatives if you do.

She: How about aspirin? Can I stop it now?

Me: …

 

As my mentor always told me, “If you don’t know what to look for, you won’t see what you should.” If I wasn’t directed through the AHA Scientific Sessions to search for the topic of women and statin therapy, I would have failed my second patient as I did my first.

But the second encounter sparked a different discussion related to cardiovascular disease prevention in women: What is the role of Aspirin in prevention? This too was discussed at Scientific Sessions 2018.

The Physicians Health Study published in 1989 demonstrated a 44% reduction in myocardial infarctions with aspirin therapy. The evidence for stroke reduction and cardiovascular deaths was inconclusive.1 The Women’s Health Study published in 2005 demonstrated a 17% reduction in stroke.2 This was primarily ischemic with an insignificant increase in hemorrhagic stroke. There was no net effect on fatal and nonfatal myocardial infarctions or overall cardiovascular deaths. The US Preventive Services’ latest statement (see link) recommends low dose aspirin for individuals between 50-59 years with a > 10% 10- year ASCVD risk and a life expectancy of at least 10 years for the primary prevention of cardiovascular disease and colorectal cancer.

Neither of my patients fit the age group; nevertheless, it is worth the pause. Would my second patient qualify in 5 years?

This year three trials on the role of aspirin in prevention were published and all conflict with these recommendations: ASPREE, ASCEND, ARRIVE. ASCEND in particular is relevant to my second patient who is diabetic rendering her ACVD risk > 20%. There was a small reduction in major adverse cardiac events and a significant increase in bleeding.3 How do we reconcile these differences. Subjects in the earlier trials had an important additional risk factor: smoking. The use of statin therapy was also significantly lower in the earlier studies. Perhaps the impact of the two accounts for the conflicting results in the more recent trials.

Is there any role for aspirin in primary prevention? Preliminary data from MESA suggests that high coronary artery calcium score and high plasma lipoprotein (a) may warrant aspirin therapy.4

Scientific Sessions offers CME. However, what we take back to our patients is far more…Aspirin or not, Statin or not, CACs or not. All these were thought provoking discussions this year.

 

I thank both my patients for consenting to using their information in this blog.

 

REFERENCES:

  1. Steering Committee of the Physicians’ Health Study Research Group. N Engl J Med 1989; 321: 129-35
  2. Ridker P, et al. A Randomized Trial of Low-Dose Aspirin in the Primary Prevention of Cardiovascular Disease in Women. N Engl J Med 2005; 352: 1293-1304.
  3. The ASCEND Study Collaborative Group N Engl J Med 2018; 379: 1529-39.
  4. Chasman D, et al. Polymorphism in the apolipoprotein (a) gene, plasma lipoprotein(a), cardiovascular Disease and Low-dose Aspirin Therapy. Atherosclersosis: 2009 Apr; 203 (2):371-6.

 

 
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Women in the New Lipid Management Guidelines

Mirvat Alasnag, MD

The American Heart Association‘s annual meeting, Scientific Sessions, remains a Mecca for cardiologists worldwide. Those of us who were unable to attend in person followed the scientific discussions virtually through the Live Streaming option.  This year the much anticipated update to the Lipid Management Guidelines were presented at the meeting.  A focus on women as a special population was addressed separately by Dr. Lynne Braun. As cardiologists, we are not trained to search for atherosclerotic cardiovascular disease (ASCVD) enhancers specific to women, namely premature menopause (less than 40 years old), pregnancy associated disorders such as preeclampsia, gestational diabetes and preterm labor. Moreover, we often fail to discuss pregnancy and contraception with women of childbearing age who require statin therapy based on their ASCVD risk assessment. The majority of our key performance indicators in a cardiac unit or clinic require that patients are discharged on a statin if they are at risk. Yet, women should be advised to discontinue statin therapy 1-2 months prior to attempting pregnancy. It seems counter-intuitive to discuss discontinuation of statin therapy in a system that measures performance by the intensity of the prescribed dose. This in itself requires retraining of cardiologists and the AHA offered a unique opportunity to highlight its importance during Dr. Braun‘s presentation.

Another related topic addressed extensively at this year’s meeting was the role of calcium scoring (CACS) in risk stratification in the new lipid management guidelines. It is noteworthy that several large studies demonstrated that CACS improves risk assessment when combined with the conventional risk parameters.1-3 Women often have lower CACS compared to age-matched men. A meta-analysis by Kavousi et al in 2016 examined 5 large cohorts of women with an ASCVD risk <7.5% (low risk by current guidelines).4  CACS was identified in 36% of the women which led to a 2-fold increase risk of ASCVD. Ensuant to this discussion, is the topic of a coronary artery calcium score of 0 that denotes a very low risk, ie 1.1–1.5% 10-year risk of ASCVD events. This is commonly referred to as the power of zero calcium.5  The latest guidelines suggest CACS may assist in further stratifying women particularly those in the intermediate and borderline categories of risk given the older age of onset of ASCVD in women. It may also assist in the shared decision making with women of different ages and women with additional risk enhancers as discussed above.

As this year’s meeting drew to a conclusion, I’m grateful I could keep pace with the discussions on lipid management in women from the other end of the globe. More importantly, as a woman cardiologist, I was able to go to work the next morning and reevaluate the discussions I have with my female patients. For the first time, I tailored my discussion on statin therapy to the woman sitting across from me, my patient.

 

References:

  1. Paixao, A.R., Berry, J.D., Neeland, I.J. et al. Coronary artery calcification and family history of myocardial infarction in the Dallas heart study. JACC Cardiovasc Imaging. 2014; 7: 679–686
  2. Elias-Smale, S.E., Proenca, R.V., Koller, M.T. et al. Coronary calcium score improves classification of coronary heart disease risk in the elderly: the Rotterdam study. J Am Coll Cardiol. 2010; 56: 1407–1414
  3. Arad, Y., Goodman, K.J., Roth, M., Newstein, D., and Guerci, A.D. Coronary calcification, coronary disease risk factors, C-reactive protein, and atherosclerotic cardiovascular disease events: the St. Francis Heart Study. J Am Coll Cardiol. 2005; 46: 158–165
  4. Kavousi, M., Desai, C.S., Ayers, C. et al. Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis. J Am Med Assoc. 2016; 316: 2126–2134
  5. Nasir, K., Bittencourt, M.S., Blaha, M.J. et al. Implications of coronary artery calcium testing among statin candidates according to american College of cardiology/american heart association cholesterol management guidelines: MESA (Multi-Ethnic study of atherosclerosis). J Am Coll Cardiol. 2015; 66: 1657–1668
  6. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol
    • Scott M. Grundy, Neil J. Stone, Alison L. Bailey, Craig Beam, Kim K. Birtcher, Roger S. Blumenthal, Lynne T. Braun, Sarah de Ferranti, Joseph Faiella-Tommasino, Daniel E. Forman, Ronald Goldberg, Paul A. Heidenreich, Mark A. Hlatky, Daniel W. Jones, Donald Lloyd-Jones, Nuria Lopez-Pajares, Chiadi E. Ndumele, Carl E. Orringer, Carmen A. Peralta, Joseph J. Saseen, Sidney C. Smith, Laurence Sperling, Salim S. Virani, Joseph Yeboah
      Journal of the American College of Cardiology Nov 2018, 25709

 
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What Do The New Lipid Guidelines Mean For Patients?

Elizabeth Knight, PhD, DNP

One of the highly anticipated stories for Scientific Sessions 2018 was the new lipid guidelines. Following the reactions on Twitter during the session, I read a lot of opinions on CAC scoring and the pros and cons of its use to further stratify those at intermediate risk. Also trending – when to target LDL-C, now that thresholds are back on the table. These are the kinds of topics that typically get a lot of attention: which drugs, which targets, which tests? Conveniently, tests and prescriptions are also reasonably easy for clinicians to implement in practice.

In addition to my work as a nurse scientist, I’m a primary care provider who works with undeserved, often uninsured patients. CAC scores are, frankly, not highly relevant to my practice (at least until you can get them for $4 at Walmart). There were, however, two aspects of the new guidelines that caught my attention as a clinician serving this population. First, that it’s officially OK to measure non-fasting lipid levels. Second, that a clinician-patient discussion is recommended before initiating statin therapy for primary prevention. While these topics may seem entirely separate,  both are highly relevant to patient experiences of care. Primary prevention of ASCVD (or any condition) hinges on clinician-patient interaction because by definition, these patients are not yet sick. They have to buy in, and they do so (or not) based on their experiences with us as their care providers. Which dose of which medication to prescribe is irrelevant if a patient does not wish to take it.

The implications of non-fasting labs for patients are not hard to grasp, but this change will particularly impact patients who face barriers to care including transportation issues and the inability to take time off work. It’s a more impactful change that seems to remove a barrier to high-quality care, and I’m glad to see it.

The risk discussion, though not new, is more complex. Per the guidelines, it should include “a review of major risk factors (cigarette smoking, elevated blood pressure, LDL-C, hemoglobin A1C, and calculated 10-year risk of ASCVD); the presence of risk-enhancing factors; the potential benefits of lifestyle and statin therapies; the potential for adverse effects and drug–drug interactions; consideration of costs of statin therapy; and patient preferences and values”. Did you get all that? Now, imagine that you don’t have any medical or scientific background. You’ve been sitting in the waiting room for an hour, you skipped breakfast because you were getting fasting labs, and you are feeling a little nervous. Your doctor is talking fast because she’s running behind. Does this sound familiar? Is the review of major risk factors going well? Is it conducive to shared decision-making and buy-in?

My point isn’t that we can’t or shouldn’t have the conversation about risk, but that we need to find effective ways to have this conversation even though we face constraints on our time. A conversation, according to Merriam-Webster online, is an “oral exchange of sentiments, observations, opinions, or ideas”. Key word: exchange. The literature shows us different ways to communicate risk to patients, although we don’t have consistent data on what works and what doesn’t, and for whom. Yet even if we identify methods for us to best communicate the information, we still need to receive information from the patient and incorporate that into our ultimate shared decision. This is not easy. It will require a broader kind of work to improve. To effectively implement these guidelines will require work to understand how patients understand and how clinicians spend limited time. These guidelines use science to guide us in what to do– now we need science to help us learn how to do it.

Image: text from “Top 10 Take-Home Messages to Reduce Risk of Atherosclerotic Cardiovascular Disease Through Cholesterol Management” displayed by frequency via WordItOut (worditout.com)

 

Source: Grundy SM, et al. 2018 Cholesterol Clinical Practice Guidelines: Executive Summary
https://www.ahajournals.org/doi/pdf/10.1161/CIR.0000000000000624

 
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Statins for Chronic Subdural Hemorrhage: Pleiotropy and Pathophysiology

Neal Parikh, MD

HMG-CoA reductase inhibitors, or statins, are widely used for lipid lowering to risk the risk of cardiovascular disease. Based on the suspected pleiotropic effects of statin medications, such as their anti-inflammatory and endothelial stabilization effects, trials of statin medications for non-cardiovascular indications have proliferated.

Statin medications have been tested for indications ranging from acute respiratory distress syndrome (ARDS) to chronic obstructive pulmonary disease (COPD). Statin therapy was not shown to be beneficial for these indications. So, I was pleasantly surprised to come across a JAMA Neurology publication reporting on a randomized trial of statin therapy for chronic subdural hemorrhage.

Subdural hemorrhage is a common and morbid condition in older individuals. To date, the primary treatment has been neurosurgical. Neurologists are involved in the care of these patients primarily to control seizures.

Jiang and colleagues report the results of a Phase II, randomized, placebo-controlled, double-blind, multi-center trial in which 169 patients with chronic subdural hematoma were randomized to receive atorvastatin or a placebo.1 They followed these patients for up to 24 weeks, and measured hematoma volume, rates of surgery, and clinical outcomes.

Although the size of the study population limits certainty in the results, their results were remarkably consistent across several outcomes, both radiographic and clinical: patients randomized to atorvastatin did better. Remarkably, patients randomized to atorvastatin also less frequently required surgery.

If confirmed, the results of this study speak to the pleiotropic effect of statin medications and inform our understanding of chronic subdural hemorrhage pathophysiology – perhaps further implicating inflammation and endothelial dysfunction. In addition to being clinically useful, these results underscore the value of persistence in clinical investigation.

 

1Jiang et al. Safety and Efficacy of Atorvastatin for Chronic Subdural Hematoma in Chinese Patients. JAMA Neurology. 2018 [E-pub ahead of print].

 

Neal Parikh Headshot

Neal S. Parikh, MD, earned his MD from Weill Cornell Medical College and completed residency training in neurology at the same institution. He is now an NIH T32 neuro-epidemiology and vascular neurology fellow at New York-Presbyterian Hospital/Columbia University Medical Center. He tweets @NealSParikhMD and contributes to Blogging Stroke as a blogger.