TREATMENT OF STABLE CORONARY ARTERY DISEASE


Control of Coronary Risk Factors
Treatment with Medications

Revascularization Procedures

        Coronary Artery Bypass Grafting
        Percutaneous Coronary Intervention (Percutaneous Transluminal Coronary Angioplasty & Stenting)
Transmyocardial Laser Revascularization
Treatment with Growth Factors

Prevention of sudden cardiac death in pts with CAD and CHF

Treatment with mutant HDL

Enhanced External Counterpulsation (EECP)

I. Control of Coronary Risk Factors including dyslipidemia-click on link for details

  1. A 5y f/u study of 48pts with mod-severe CAD randomized to intensive lifestyle changes (diet, exercise, and behavioral components) vs. "usual care" showed sig. decreases in fat intake, LDL levels, use of lipid-lowering drugs, frequency of angina, major cardiac events, and revascularization, and sig. greater improvement in angiographic measures of CAD (JAMA 280:2001, 1998--JW)

II. Treatment with medications

  1. Aspirin for prevention of coronary events--Click link for details
  2. Warfarin
    1. A meta-analysis of 31 clinical trials involving > 11,000 pts of warfarin anticoagulation (which were categorized according to intensity of anticoagulation used and whether the controls got no antithrombotics or got ASA, and which did not differentiate pts who had or had not had MI) found:
      1. For "High-intensity" (target INR 2.8-4.8) and "Moderate-Intensity" (target INR 2-3) anticoagulation vs. placebo, sig. reductions in mortality, MI, & thromboembolic complications inv. CVA
      2. For "High-intensity" and "Moderate-intensity" anticoagulation vs. ASA, no sig. reductions in mortality, MI, CVA, or combination of all 3 were seen
      3. For "High-intensity" and "Moderate-intensity" anticoagulation + ASA vs. ASA alone, no sig. reduction in mortality, MI, or CVA were seen; but there was sig. reduction in combined endpoint of all 3 (RR 56%)
      4. For "Low-intensity" (target INR < 2) anticoagulation + ASA vs. ASA alone, no sig. reduction in mortality, MI, or CVA were seen
    1. Warfarin after CABG
      1. The Post CABG Trial rnadomized 1351 pts s/p CABG to warfarin adjusted to INR < 1.5 vs. placebo; the original trial (NEJM 336:153, 1997), with a 4y f/u, showed no sig. benefit to warfarin; a f/u study of the same pt groups (Circ. 102:157, 2000), which extended f/u to 7.5 post-randomization, showed statistically sig. reductions in total mortality (35% reduction) and MI's (34% reduction) in the warfarin group.
    2. See also under "Acute MI" for discussion of Warfarin in post-MI patients
  1. Clopidogrel after percutaneous coronary intervention (PTCA/stent)
    1. Short-term use after PCI in addition to ASA is associated with lower incidence of thrombotic complications than ASA alone
    2. In a randomized trial of 2116 pts undergoing percutaneous coronary intervention randomized to usual care (clopidogrel 75mg QD starting after PCI through day 28 then placebo) vs. an extended regimen (clopidogrel 300mg 3-24h before PCI then 75mg QD x 12mos); all received ASA 81-325mg QD at discretion of investigator; at 1y, RR of 0.73 (sig.) for (death, MI, or CVA); reduction in 28d incidence of same endpoint was limited to those pts who received clopidogrel at least 6h before PCI; risk of major bleeding over 1y was not sig. diff. between the two groups ("CREDO" trial; JAMA 288:2411, 2002--abst)
    3. After placement of drug-eluting stents
      1. In an observational study of a cohort of 746 pts who had undergone either drug-eluting or bare metal coronary stenting and who were treated with clopidogrel x 6mos post-procedure, drug-eluting stent recipients had sig. higher incidence of (cardiac death or MI) between months 7-18 than bare metal stent recipients (4.9% vs. 1.3%) (J. Am. Coll. Cardiol. 48:2584, 2006--JW)
      2. In an observational study in a cohort of 4,666 pts undergoing coronary stenting, among those who received drug-eluting stents and who had no major events during first 6mos, longer-term use of clopidogrel was associated with sig. lower 2y incidence of death (2% vs. 5.3%); no diff. seen based on clopidogrel use or non-use in bare metal stent recipients (JAMA 297:159, 2007--JW)
  2. Organic Nitrates reduce symptomatic angina
  3. Beta-Blockers reduce symptomatic angina; may reduce risk of MI
  4. Calcium channel blockers reduce symptomatic angina and may reduce risk of coronary events
    1. 97 pts with positive exercise treadmill test with no change on ETT findings after starting atenolol 50/d and SL NTG PRN were randomized to amlodipine 5mg QD vs. Diltiazem 90mg BID x 8 wks. After 4wks if angina was still present, dose was doubled. Neither drug affected HR significantly. Both groups had reduction in angina sx. Dilt group had higher incidence of adverse effects inc. syncope & bradycardia (Am. J. Cardiol 81:133, 1998--AFP)
    2. 7,665 patients with stable angina randomized to long-acting nifedipine 60mg QD vs. placebo; after 5y mean f/u, no sig. diff in incidence of (death, MI, refractory angina, new heart failure, CVA, or peripheral revascularization) and of each individual endpoint, except heart failure, the incidence of which was sig. lower in the nifedipine group ("ACTION" trial; Lancet 364:849, 2004--JW)
    3. 1,991 pts with CAD and DBP < 100 mm Hg (mean DBP 77; 60% were diagnosed with HTN) randomized to amlodipine 10mg/d, enalapril 20mg/d, or placebo. Over 24mo f/u, incidence of (revascularization, angina hospitalization, MI, or CVA) was sig. lower in amlodipine group vs. placebo (HR 0.69); the significant reduction was upheld in the subgroups of pts with SBPs both above & below the mean.  Incidence of the combined endpoint was not sig. diff. for amlodipine vs. enalapril or enalapril vs. placebo. No sig. diff. in degree of BP lowering with the two drugs ("CAMELOT" study, JAMA 292:2217, 2004)
  5. ACE Inhibitors
    1. The "HOPE" trial showed a mortality benefit with use of Ramipril in patients with stable CAD or other vascular disease--Click HERE for details
    2. 12,218 pts with stable CAD and no HF randomized to perindopril 8mg PO QD vs. placebo.  Over mean 4.2y f/u, risk of (CV death, nonfatal MI, or resuscitated cardiac arrest) was sig. lower in perindopril recipients (8% vs. 10%).  Effect held up in analysis of subgroups on beta-blockers, lipid-lowerin drugs, or Ca-blockers; also among diabetics and normotensive pts (Lancet 362:782, 2003--JW)
    3. 8, 290 pts with stable CAD and normal LVEF randomized to trandolapril 4mg/d vs. placebo; over median 5y f/u, incidence of (cardiovascular death, nonfatal MI, or coronary revascularization) was not sig. diff. between thr groups; subgroup analysis did not reveal a subgroup who benefited from trandolapril ("PEACE" Trial; NEJM 351:2058, 2004--JW)
    4. Negative findings in CAMELOT trial (click on link for details)
    5. In a meta-analysis of seven randomized trials involving about 34,000 pts pf ACEIs vs. placebo for pts with stable CAD or high risk for CAD but no heart failure or LV dysfunction, ACEI recipients had sig. lower incidence of all-cause mortality (RR 0.86), cardiovascular mortality (RR 0.81), MI (RR 0.82), and CVA (RR 0.77) (Arch. Int. Med. 166:787, 2006--JW)
    6. In a meta-analysis of 3 randomized trials (with total 29,805 pts) comparing ACE inhibitors vs. placebo in pts with coronary artery disease but no HF, over mean 4.5y f/u, ACEI therapy was associated with sig. lower incidence of all-cause mortality (7.8% vs. 8.9%) and composite of cardiovascular mortality, nonfatal MI, or CVA (10.7% vs. 12.8%). (Lancet 368:581, 2006--JW)
  6. Ranolazine (Ranexa)
    1. A "fatty acid oxidation inhibitor"
    2. Can prolong QTc, especially in pts with hepatic dysfunction
    3. 823 pts with symptomatic chronic stable angina already on atenolol, amlodipine, or diltiazem randomized to ranolazine 750-1000mg BID vs. placebo x 12wks; active-tx groups had sig. greater increases in treadmill exercise time and sig. greater reductions in angina frequency ("CARISA" trial; JAMA 291:309, 2004--abst)
    4. Associated with increased QT interval
  7. Antibiotics--See also section on Managenent of Acute MI
    1. Rationale is based on studies showing high incidence of Chlamydia pneumoniae within atherosclerotic placques
    2. 60 pts s/p MI w/high Ab levels against C. pneumoniae randomized to azithromycin vs. placebo; rates of adverse CV events at 18mos were 8% in tx group vs. 25% in plaebo group (nonsig.) (Circ. 96:404, 1997-JW)
    3. 302 pts with CAD and serologic evidence of C. pneumoniae exposure randomized to azithromycin 500mg/d x 3d then 500mg/wk x 3mos vs. placebo; at 2y, no diff. in incidence of cardiac events between the two groups ("ACADEMIC" study; Circ. 102:1755, 2000--JW)
    4. Azithromycin (600mg/d x 3d then 600mg/wk x 12wks) vs. placebo was ass'd with no sig. difference in (nonfatal MI, coronary revascularization, hospitalization for angina, or all-cause mortality) over median 14mo f/u  in a randomized trial in 7747 adults with prior MI and known Chlamydia pneumoniae exposure (IgG titer > 1:8) (JAMA 290:1459, 2003--abst)
    5. In a meta-analysis of 9 randomized trials of abx for secondary prevention of coronary events, no overall benefit was seen in risk of cardiovascular events or mortality (Arch. Int. Med. 164:2156, 2004--abst)
    6. In a meta-analysis of 11 randomized trials of anti-chlamydial abx in pts with known CAD for prevention of MI and mortality, there was no sig. diff. in risk of either outcome (JAMA 293:2641, 2005--abst)
    7. In a study in 4,373 pts with stable CAD randomized to clarithromycin vs. placebo x 2wks, over mean 2.5y f/u, incidence of (death or nonfatal cardiac events) was not sig. diff. between the two groups, but all-cause mortality was sig. more common in the clarithromycin recipients (HR 1.27) (BMJ 332:22, 2006--JW)
  8. Consider fish or fish oil
  9. Allopurinol
    1. Shown effective at reducing symptoms and improving exercise performance c/w placebo in a 6wk randomized study in 60 pts iwth stable angina.  Dose was 100mg QD x 1wk then 300mg QD x 1wk then 300mg BID (paper presented at European Society of Cardiology conference, FP news 10/15/09)

III. Revascularization procedures

  1. Coronary Artery Bypass Grafting ("CABG")
    1. Indications for, per ACC/AHA, divided into strength-of-evidence "classes", are published in Circ. 100:1464, 1999--AFP
    2. In a study of 200 pts randomized to CABG off-pump or on-pump (i.e. w/cardiopulmonary bypass); at 1y, there was no sig. diff. in health-related quality of life, graft patency, death, CVA, MI, and reintervention. (JAMA 291:1841, 2004--abst)
    3. Pexeilzumab (a C5 complement inhibitor) for prevention of perioperative MI in patients undergoing CABG
      1. In a randomized trial of 3099 pts underoing CABG (353 also underwent valve surgery at the same time) randomized to pexelizumab vs. placebo starting 10min before surgery, incidence of (death or MI within 30d) was sig. lower in pexelizumab group (11.5% vs. 14.0%), though no sig. diff. in the subgroup of 2,735 pts undergoing CABG only (JAMA 291:2319, 2004--abst)
    4. Venous vs. radial grafts
      1. In a study of 561 pts with triple-vessel CAD randomized to (nonemergent) CABG radial artery vs. saphenous vein graft for either right coronary or left circumflex coronaries, incidence of graft occlusion at 8-12mo f/u was sig. less common with radial aa. grafts (8.2% vs. 13.6%) (NEJM 351:2262, 2004--JW)
  1. Percutaneous transluminal coronary angioplasty ("PTCA") and stenting (collectively referred to as Percutaneous Coronary Intervention or "PCI")
    1. Palmaz-Schatz intracoronary stenting as an adjunct to PTCA
      1. PTCA plus stent ass'd with higher 6mo patency rates than PTCA alone for restenosis after PTCA (NEJM 339:1702, 1998--JW)
      2. Better for prevention of cardiac events than PTCA for occluded venous coronary grafts (NEJM 337:740, 1997—JW)
      3. Drug-Coated stents
        1. Reduce neointimal hyperplasia that can lead to restenosis
        2. Drugs used
          1. Paclitaxel--A microtubule inhibitor that limits cell division and migration
          2. Sirolimus (Rapamycin) and Everolimus--Immunosuppressives that inhibit proliferation of vascular smooth muscle cells
          3. Zotarolimus (may be associated with  higher likelihood of in-stent thrombosis than other drug-coated stents)
          4. Everolimus
        3. Studies of drug-eluting stents--Click HERE for details on individual studies
          1. Meta-analyses of drug-eluting vs. bare-metal stents
            1. In a meta-analysis of 14 studies involving 6,675 patients randomized to drug-eluting vs. bare-metal stents, the 1y incidence of thrombosis was sig. greater in the drug-eluting stent pts (Am. J. Med. 119:1056, 2006--JW)
            2. In a meta-analysis of four trials of sirolimus-eluting stents vs. bare-metal stents, 4y incidences of overall mortality and of MI were not sig. diff. between the two groups, though in subgroup of pts with DM, sirolimus-eluting stents were associated with sig. increased overall mortality (12.2% vs. 4.4%) (NEJM 356:989, 2007--JW)
            3. In a meta-analysis of five trials of paclitaxel-eluting stents vs. bare-metal stents, there were no sig. diffs. in 4y incidence of mortality or MI though target-vessel revascularization was sig. less common in the recipients of paclitaxel-eluting stents (HR 0.62). (NEJM 356:998, 2007--JW)
            4. In a meta-analysis of 14 trials of sirolimus-eluting stents vs. bare-metal stents of duration at least 1y, there was no sig. diff. in incidence of (death or MI) or stent thrombosis (NEJM 356:1030, 2007--JW)
          2. Sirolimus vs.paclitaxel:
            1. In a meta-analysis of 6 randomized studies in 3,669 pts with CAD randomized to sirolimus- vs. paclitaxel-eluting stents, over min. 6mo f/u, sirolimus stents were associated with sig. lower incidence of target lesion revascularization (5.1% vs. 7.8%), but no sig. diff. in cardiac events, mortality, or MI (JAMA 294:819, 2005--abst)
            2. In a study in 1,386 pts with one or two coronary artery lesions randomized to sirolimus-eluting vs. paclitaxel-eluting stents, there was no sig. diff. in 8mo incidence of restenosis or 12mo incidence of target-lesion revascularization (JAMA 295:895, 2006--JW)
            3. In a study in 607 pts undergoing percutaneous coronary intervention for left main coronary artery stenoses randomized to paclitaxel-eluting vs. sirolimus-eluting stents, there was no sig. diff. in 1y incidence of (death, MI, or target-lesion revascularization) (J. Am. Coll. Cardiol. 53:1760, 2009-JW)
          3. Oral sirolimus was shown to be associated with better angiographic outcomes in stented pts in one randomized trial ("OSIRIS" trial; Circ. 110:790, 2004--abst)
          4. In a trial in 300 pts with in-stent restenosis randomized to balloon angioplasty vs. sirolimus-eluting stent vs. paclitaxel-eluting stent, 6mo incidence of angiographic restenosis was sig. lower in both sirolimus- and paclitaxel-eluting stent groups c/w balloon-angioplasty group (14.5% and 21.7% vs. 44.6%) and incidence of target-vessel revascularization was as well (8% and 19% vs. 33%); revascularization but not angiographic restenosis incidences were sig. lower in sirolimus group than paclitaxel group (JAMA 293:165, 2005--abst)
          5. Drug-eluting stents in acute MI
    2. Rotational atherectomy as an adjunct to PTCA
      1. Used to excise coronary atheromata; usually done in conjunction w/intracoronary u/s
      2. In the Stent Versus Directional Coronary Atherectomy Randomized Trial ("START"), 122 pts w/CAD suitable for either procedure were randomized to PTCA + stenting vs. atherectomy. At 6mo f/u, restesosis rates sig. lower in atherectomy group (32.8% vs. 15.8%) (JACC 34:1050, 1999--AFP)
    3. Intracoronary radiation to reduce restenosis rate after PTCA
      1. Radiation shown to be ass'd with lower rates of restenosis-requiring-revascularization vs. placebo (15% vs. 48%, sig.) in a randomized trial in 55 pts undergoing 2nd PTCA (after restenosis following 1st) and followed for 3y; no sig. diff. in mortality (Circ. 101:360, 2001--JW)
      2. Radiation ass'd with dose-dependent reductions in 6mo restenosis rates only in pts not receiving stents in a randomized trial of 181 pts undergoing PTCA of previously untx'd coronary stenoses; 51 pts also received stents (NEJM 344:243, 2001--JW)
      3. Radiation ass'd with sig. less need for revascularization over 9mo f/u (24% vs. 42%) in a randomized study of 252 pts receiving PTCA or atheroablation and in most cases, restenting, for restenosis after stenting; but late MI was nonsig. more common in radiation group (10% vs. 4%) (NEJM 344:250, 2001--JW)
    4. Homocysteine-lowering therapy after PTCA may reduce restenosis rate
      1. 553 pts undergoing PTCA (about 50% also received stents) randomized to (1mg folate + 400ug B12 + 10mg B6 QD) vs. placebo x 6mos; at 1y, active tx was ass'd with RR of  0.65 (15% vs. 23%, sig.) for (revascularization, MI, or death) ("Swiss Heart Study," JAMA 288:973, 2002--JW)
      2. However, in another randomized study in 636 pts s/p successful PTCA, 6mos or oral folate c/w placebo was ass'd with sig. reduction in mean serum homocysteine level, but sig. higher incidence of restenosis and revascularization procedures on the target vessels (NEJM 350:2673, 2004--JW)
  1. CABG vs. PCI
  1. CABG vs. PTCA w/o stenting
    1. In a study in 1829 pts with avg. 3.5 vessel disease randomized to PTCA or CABG, no sig. diff. in in-hosp mortality or 5y  incidence of QWMI or mortality BUT among pts with DM (19% of cohort), 5y survival sig. better with CABG (81% vs. 66%); subsequent analysis showed this advantage to come solely from reduced rate of cardiac mortality. Also, advantage seemed to be limited to those CABG pts who had grafts with IMA as opposed to saphenous v.  Additional revascularization nec. in 8% with CABG vs. 54% with PTCA over 5y ("Bypass Angioplasty Revascularization Investigation"; NEJM 335:217, 1996)
    2. In a study in 1829 pts with multivessel CAD and clinically severe angina or ongoing ischemia (41% had triple-vessel dis; 63% had unstable angina) randomized to PTCA vs. CABG and f/u for 5y, angina free at 5y: 85% CABG; 79% PTCA; 57% of CABG vs. 76% of PTCA pts were using anti-ischemic meds at 5y (JAMA 277:715, 1997óJW)
  2. CABG vs. PTCA + stenting
  1. 1205 pts with multivessal CAD w/o h/o prior revascularization randomized to CABG vs. stenting.  Over 1y f/u, stenting pts were sig. more likely to need additional revascularization procedures (21% vs. 3.8%) and sig. less likely to be angina-free (79% vs. 90%); no sig. diff. in risk of death, CVA, or MI ("Arterial Revascularization Therapy Study," NEJM 344:1117, 2001--JW)
    1. In a paper reporting 3y f/u of the same cohort, diff. in incidence of repeat revascularization remained sig. (20% vs. 6% with stenting vs. CABG), and CABG pts continued to have sig. less angina and need for anti-anginal drugs; also, still no sig. diff. in incidence of death, CVA, or MI (Circ. 109:1114, 2004--JW)
  2. 988 symptomatic pts with multivessel CAD randomized to CABG vs. PTCA + stenting (mean # of vessels needing revascularization was 2.8).  Over median 2y f/u, CABG group had sig. lower incidence of revascularization (6% vs. 21%) and sig. higher incidence of all-cause mortality (4.5% vs. 1.6%) but no sig. diff. in incidence of (death or Q-wave MI) ("SoS" trial; Lancet 360:965, 2002--JW)
  3. 220 pts with isolated high-grade LAD stenosis of 75% of more and normal ventricular function randomized to stent vs. "minimally invasive" CABG with IMA.  At 6mos, CABG pts had sig. less angina prevalence (21% vs. 38%) and sig. less incidence of revascularization (8% vs. 29%) (NEJM 347:561, 2002--JW)study in 220 pts with isolated proximal LAD stenosis o randomized to IMA graft vs. bare-metal stant implantation, after 5y
    1. In a paper reporting 5y f/u of the same cohort, 5y incidence of (death, reinfarction, or target-vessel revascularization) was sig. lower in the surgery group (29% vs. 47%) (Circ. 112:3445, 2005--JW)
  4. In a prospective study of 6,033 pts with multivessel CAD who underwent percutaneous coronary interventions (PCI) vs. CABG, 1y and 5y all-cause mortality, after adjusting for baseline differences, were sig. higher with PCI.  The study sample predated the use of drug-eluting stents (Circ. 109:2290, 2004--JW)
  5. In a meta-analysis of PTCA + stenting vs. minimally invasive CABG  for pts with isolated LAD stenosis, stenting recipients had sig. higher incidence of recurrent angina (OR 2.62), major cerebral or coronary events (OR 2.86), and need for coronary revascularization (OR 4.63) but no sig. diff. in mortality (BMJ 334:617, 2007--JW)
  6. In a study in 1,800 pts with either left main or 3-vessel coronary disease randomized to CABG vs. percutaneous coronary intervention, 1y incidence of (death, CVA, MI, or repeat revascularization) was sig. lower in the CABG group (12.4% vs. 17.8%) ("SYNTAX" trial; NEJM 360:961, 2009-JW)
  1. PCI vs. Medical Management--Seems to improve symptoms but not incidence of mortality or MI
  1. Randomized Trials
    1. 1020 pts w/angiographically proven CAD (most single- or double-vessel, 50% had had previous MI) randomized to PTCA vs. medical management; at f/u (median 2.7y), risk of death or MI sig. greater in PTCA group (6.3% vs. 3.3%), mostly due to procedure-related events. However, sx (angina, SOB, ex. tol.) sig. better in PTCA group (most benefit in pts w/severe sx at baseline) (Lancet 350:461, 1997—JW)
    2. 44 stable post-MI pts (with "large area of myocardium in jeopardy on nuclear scanning" and coronary lesions amenable to PTCA on angio; excluded pts with sig. left main or multivessel dis.) randomized to PTCA vs. intensive medical therapy (nitrates, beta- and/or Ca-blockers, ASA, and lipid-lowering drugs). At avg. 6wk f/u, repeat nuclear scanning showed similar reductions in amount of "myocardium in jeopardy" in both groups. At avg. 12mo f/u, both groups had similar rates of cardiac events (17% w/med. therapy and 14% with PTCA) (Circ. 98:2017, 1998--JW)
    3. 341 pts with single- or double-vessel disease (but no left main disease), stable angina, LDL > 115, and no CHF randomized to PTCA + "usual" lipid care vs. no PTCA but aggressive lipid management (Atorvastatin 80mg/d). The non-PTCA group had sig. fewer ischemic events over 18mo f/u (13% vs. 21%) though most of the diff. due to less worsening angina resulting in hosp; no diff. in cardiac death or MI (NEJM 341:70, 1999--JW)
    4. 301 pts > 75yo with chronic stable angina despite tx with at least 2 anti-anginal drugs randomized to "optimized" medial therapy vs. invasive therapy. At 1y f/u, quality-of-life changes were similar in the 2 groups; the invasive group had sig. fewer rehospitalizations for revascularization (10% vs. 46%) but there was no sig. diff. in 1y all-cause mortality. 1y incidence for (death, nonfatal MI, or hospitalization for acute coronary syndromes) was sig. lower in the invasive group (25.5% vs. 64.2%) ("TIME" trial, JAMA 289:1117, 2003--JW)
    5. In a 7y study of 1,018 pts randomized to PTCA vs. medical therapy for stable CAD (60% had single-vessel disease, only 9% underwent stenting), there were no sig. differences in primary endpoint of (death or MI), incidence of CABG, or all-cause mortality but at 7y, anginal sx were less and exercise tolerance was greater in the PTCA group. ("RITA-2" trial; J. Am. Coll. Cardiol. 42:1161, 2003--JW)
    6. In a 1-year study of 101 men > 70yo with stable angina and 75% or greater stenosis of at least 1 (non_LAD) coronary artery and normal LVEF randomized to PTCA + stenting vs. an exercise program, incidence of (death or coronary event, including revascularization or hospitalizations for worsening angina) was sig. lower in exercise group (12% vs. 30%) (didn't get ref! ER)
    7. In a study in 2,287 pts with stable CAD & > 70% stenosis + objective evidence of ischemia or > 80% stenosis + classic angina; all with LVEF > 29%) randomized to PCI + optimal medical therapy vs. optimal medical therapy alone, over median 4.6y f/u, there was no sig. diff. in incidence of (death or MI) or hospitalization for ACS or hospitalization for CVA. PCID group had ig. lower incidence of revascularization (21% vs. 33%) ("COURAGE" Trial; NEJM 356:1503, 2007-JW)
    8. In a study in 201 patients with MI in prior 3mos and silent ischemia and 1-2 vessel CAD randomized to PCI vs. drug therapy alone (all pts received ASA + a statin), over mean 10.2y f/u, incidence of major adverse cardiac events was sig. lower in PCI group (HR 0.33, absolute reduction rate of 6.3% per year) (" Swiss Interventional Study on Silent Ischemia Type II" ("SWISSI II") Trial; JAMA 297:1985, 2007--abst)
    9. 2,368 pts with type 2 DM and CAD randomized to either "prompt revascularization" or medical therapy AND also (in a 2 x 2 approach) to glycemic management with (insulin or a sulfonylurea) vs. (metformin or rosiglitazone). Over mean 5.3y f/u, there was no sig. diff. in mortality among any of the treatment groups or incidence of major cardiovascular events; incidence of revascularization was sig. lower in pts who received CABG vs. medical terhapy (69.5% vs. 77.6%) (NEJM 360:2503, 2009-JW)
  2. Meta-analyses
    1. In a meta-analysis of 6 randomized trials of medial therapy vs. PTCA for stable CAD in total 1904 pts, PTCA was ass'd with sig. lower risk for angina (RR 0.7) but sig. higher risk for eventual CABG (RR 1.59) and nonsig. higher risk for MI (RR 1.42), death (RR 1.32), and subsequent PTCA (RR 1.29) (BMJ 321:73, 2000--JW)
    2. In a meta-analysis of 11 randomized trials comparing percutaneous coronary interventions with conservative treatment in pts with stable CAD, there were no sig. diffs. in overall mortality, (cardiac death or MI), nonfatal MI, CABG, or PCI during f/u.  In subset of pts with MI in the prior 3mos, PCI was associated with sig. benefit (RR 0.4) (Circ. 111:2906, 2005--abst)
  3. Studies of PCI of infarct-related arteries in post-MI patients
    1. In a study in 2,166 pts 3-28d s/p acute MI with poor or absent flow in a major infarct-related artery and LVEF < 50% and moderate or greater retained myocardial viability in the corresponding area of myocardium, randomized to PCI (87% got stents, only 8% drug-eluting) vs. medical treatment only, there was no sig. diff. in iincidence of (death, nonfatal MI, or admission with NYHA class IV HF) ("Occluded Artery Trial" ("OAT"); NEJM 355:2395, 2006-JW)
    2. In a subgroup analysis of OAT trial subjects who were enrolled < 3d after their MI and < 7d after their MI, there was also no benefit with PCI in incidence of (death, nonfatal MI, or NYHA class IV HF) (Eur. Heart J. 30:183, 2009-JW)

IV. Transmyocardial Laser Revascularization

  1. Laser used to create channels through myocardial wall to the ventricular lumen, for patients who are not good candidates for PTCA or CABG
  2. Can be done through transthoracic or percutaneous approach
  3. Clinical trial data
    1. A systematic review of 6 the published RCTs of open TMR vs. medical therapy revealed that none were blinded, two allowed patients failing medication-only therapy to cross over to the TMR group, and many used subjective measures of disease severity, rather than objective ones.  Many of the objective measures included in these studies did not show an advantage with TMR.  No mortality reduction has been seen with TMR.  In contrast, studies of TMR as an adjunct to coronary artery bypass grafting have suggested a survival advantage over up to 1 year of follow-up.  There have been four RCT's of percutaneous TMR. (J Am Coll Cardiol 41:173, 2003)

V. Treatment with Growth Factors

  1. In an uncontrolled study of 5 patients with severe CAD receiving intramyocardial injection of DNA coding for an endothelial growth factor, rapid functional improvement and improved myocardial perfusion was seen in all patients (Circ. 98:2800, 1998--JW)
  2. In a study in 114 pts with ST-segment-elevation MI who had undergone successful reperfusion randomized to granulocyte colony-stimulating-factor vs. placebo, there was no sig. diff. in change in ventricular function or in infarct size (JAMA 295:1003, 2006--JW)

VI. Prevention of sudden cardiac death in pts with CAD and CHF--see under "Congestive Heart Failure"

VII. Treatment with mutant HDL

  1. Infusion IV with a mutant form of HDL ("ETC-216," has 1 amino-acid substitution; found in a community in Northern Italy with long life-spans) was ass'd with sig. regression of atherosclerosis in a placebo-controlled randomized trial in 45 pts 30-75 with CAD (JAMA 290:2292, 2003--JW)

VIII. Enhanced External Counterpulsation (EECP)

  1. A noninvasive treatment in which inflatable cuffs are worn on the legs and buttocks.  The cuffs inflate with each diastole, assisting blood return to the right side of the heard and increasing coronary perfusion pressure.

IX. See also Bone Marrow Cell Transfer after MI (click link for details)