June 18th, 2010

Is Optimal Medical Therapy Really Optimal?

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A 61-year-old man with a past medical history significant for hypertension, hyperlipidemia (LDL-C, 145 mg/dL; HDL-C, 38 mg/dL), and type 2 diabetes (HbA1c, 8.2) presents to his primary care physician after several months of exertional chest tightness that is associated with dyspnea and relieved by rest. His current medications include lisinopril at 20 mg/day, metoprolol succinate at 50 mg/day, simvastatin at 20 mg/day, and glyburide at 10 mg/day.

He is referred for an exercise treadmill test with myocardial perfusion imaging. He exercises for 8:08, achieving 10.2 METs and reaching 94% of peak HR goal, before stopping for mild chest tightness and fatigue. The imaging portion of the study reveals an estimated LVEF of 62% with moderate-sized, medium-intensity reversible perfusion defects in both the inferior and lateral walls.

Based on these results, the patient is referred for coronary angiography, which reveals 70% discrete lesion of the mid-LAD after the take-off of the first diagonal, 90% complex lesion of the mid-LCx, and 80% discrete lesion in the proximal RCA.

Questions for Discussion:

1.   How would you proceed at this point?

  • Optimize medical therapy with intensification of glycemic, anti-hypertensive, and lipid-lowering therapies.
  • Optimize medical therapy but also proceed with PCI and stenting of the RCA and LCx.
  • Optimize medical therapy and proceed to PCI based on fractional flow reserve assessment.
  • Optimize medical therapy and refer the patient for CABG surgery.

2.   What would constitute “optimal medical therapy” for this patient?

3.   Based on the patient’s clinical presentation, would you have performed the sequential testing as outlined in the vignette (i.e., stress test followed by coronary angiography), or would you have pursued a different management strategy?

Response:
James Fang, MD

Therapy for this patient is very much dependent on the goals of the patient as well as his physicians. Clearly, medical therapy needs to be intensified. The decision to catheterize the patient based on the stress test results would likely have been driven by a concern for multivessel ischemic heart disease, despite the good exercise tolerance, and by a perception that revascularization in this setting (with preserved ventricular function) improves survival. This decision of whether or not to revascularize depends on the ischemic burden. If the patient is not satisfied with his functional capacity and is limited by angina, I would offer revascularization. Contemporary revascularization trials suggest no significant mortality differences between CABG and PCI, even in the presence of DM. However, more procedures are likely with a PCI approach.

Medical management should consist of aggressive statin therapy to drive his LDL to <70 mg/dL, his HDL to >40 mg/dL, and his TG to <200 mg/dL. I suspect a potent statin will be necessary to achieve these levels — and if that isn’t effective, I would consider niacin, even though the trial results aren’t in yet. His HbA1c goal is unclear, particularly in light of the recent ACCORD data. I would personally target <7.5%, but this is a compromise based on the available data. Clearly, overly aggressive control has to be balanced against complications from hypoglycemia — an issue that has tempered the trials of glucose control in heart disease. The best way to control blood sugar is not clear from the diabetes trials, and most patients seem to require more than one class of oral hypoglycemic drug to reach good control. Finally, this patient’s beta-blocker dose is very modest and could be increased.

A case could certainly have been made to manage the patient medically, based purely on the stress test results. However, in the U.S., it is rare for a positive stress test to not lead to coronary angiography, despite good evidence that even patients with multivessel ischemic heart disease can be managed medically without sacrificing years of life.

4 Responses to “Is Optimal Medical Therapy Really Optimal?”

  1. As always, it depends
    What percentage of his myocardium is ischemic with stress imaging? If it is less than 10%, I am not familiar with any literature that would suggest a benefit of revascularization. If more than 10% of his myocardium is ischemic with stress imaging, Courage as well as a retrospective analysis in Circulation a few years ago would suggest a benefit from stenting. I do not see a role for CABG based upon the information provided.—————————————————————Optimal Medical Management would be getting a Hgb A-1-C to less than 6.5 using diet and exercise plus meds not likely to cause hypoglycemia including metformin, TZD, and if this is not enough, consider a dpp-4 inhibitor. I would get his LDL to <70 and his HDL to around 70 with the combination of statin, niacin er, at least 2,000mg of fish oil derived omega-3 fatty acid (unless his triglycerides were elevated in which case I would use 4,000 mg omega-3), and zetia if needed. ———————-In addition, I would check a Vit D level and replace with D-3 to achieve a blood level of 50-70. I would check a testosterone level and if low would initiate supplementation. I would make sure he did not have sleep apnea or periodontal disease, I would encourage that he eat a ton of green vegetables and pigmented fruits, get regular moderate exercise, and modify stress. ——————To encourage compliance and monitor response to therapy, I would do a baseline EBT CAC score and in one year repeat it. If his annual calcified plaque progression was >14% I would tighten up on the preventive strategies.

  2. switching to evidence-based therapies
    Lisinopril has no hard outcome evidence – I would use ramipril or perindopril. I would also switch his simva to either atorvastatin or rosuvastatin, his glyburide to metformin with addition of pioglitazone (PROACTIVE), add aspirin, and possibly clopidogrel as well. I agree with William that he needs HDL-raising – likely niacin. Diabetes with 3vd used to be a hard indication for CABG, but nowadays – with optimal medical therapy being what it is – that is much less assured. I would also track this man’s plaque burden with serial measurements, and titrate therapy to achieve plaque regression, regardless of whether he is submitted to revascularization or not. If his BP was not controlled, I would renin/aldo profile him. I would also do an Lp(a) and TSH measurement.

  3. Dr. Fang, how can you say “I would consider niacin, even though the trial results aren’t in yet”

    Do the HATS and FATS trials not exist? Have these trials been shown to be invalid. These are very powerful prospective trials that clearly put niacin plus LDL lowering as far superior to LDL lowering alone.

  4. In the spirit of full disclosure, I am a big fan of niacin but I don’t believe we have definitive trial evidence yet. FATS (1990) and HATS (2001) were small (<200 pts) with primary angiographic endpoints. Yes, there was compelling evidence for clinical benefit for niacin but statin use was modest in both studies and not the high dose that most recommend. I anxiously await AIM-HIGH which is a >3000 pt trial of simva + niacin.