Det verkar gå bättre för patienter med typ 1-diabetes och som har förträngningar i flera kranskärl om de får kranskärlskirurgi snarare än ballgongvidgning, enligt en stor svensk registerbaserad studie.
 
– Fyndet är ganska väntat men ingen har kunnat visa detta tidigare. Samtidigt pekar våra resultat på att det bara är en försvinnande liten andel av de här patienterna som behandlas kirurgiskt. Här finns en stor förbättringspotential, säger Martin Holzmann, docent och överläkare vid Karolinska universitetssjukhuset i Huddinge.

Han presenterar studien som en så kallad ”late breaker” i dag, lördag, på ESC-kongressen i Barcelona. En ”late breaker” är en studie som förväntas påverka klinisk praxis.
Resultaten visar att patienter som opereras med bypasskirurgi i mindre utsträckning drabbas av hjärtrelaterad död, hjärtinfarkter och har mindre behov av nya invasiva åtgärder för att öppna upp kranskärlen, jämfört med de patienter som genomgår det skonsammare ingreppet ballongvidgning, PCI.

Tidigare forskning, bland annat i form av randomiserade studier, har visserligen visat att diabetespatienter med mer komplex kranskärlssjukdom tjänar på att bli revaskulariserade med kirurgi. Men i denna forskning har det inte gått att få fram resultaten specifikt för typ 1-diabetes som i grunden är en annan biologisk sjukdom än den till antalet patienter dominerande sjukdomen typ 2-diabetes. Den senare svarar för runt 90 procent av alla diabetesfall.

– När vi nu ser tillbaka i våra svenska registerdata från 1995 och framåt och bara tittar på patienter med typ 1-diabetes, totalt över 2 500 individer, så är bilden samstämmig med resultaten från de randomiserade studierna, säger Martin Holzmann.

Det möjligen mest uppseendeväckande i den nya svenska studien är att under den senare delen av undersökningen så var det bara 5 procent av patienterna med typ 1-diabetes som behandlades med kirurgi – vilket av allt att döma alltså är den bästa åtgärden.

– Det har längre funnits en underbehandling med kranskärlskirurgi vid diabetes. Men situationen verkar vara extrem just vid typ 1-diabetes. En möjlig orsak kan vara att sjukvårdspersonal felaktigt uppfattar typ 1-diabetes som en mindre farlig sjukdom än typ 2-diabetes när det egentligen är tvärtom, säger Martin Holzmann.
Studien är av observationstyp och har som svaghet att den därför inte kan fastslå orsaksamband.

– Vi försöker vara försiktiga i tolkningarna. Vi ser att sjukare patienter i högre utsträckning fick PCI och även om vi använder statistiska metoder för att jämna ut dessa skillnader så fanns det sannolikt skillnader kvar som var okända för oss, säger Martin Holzmann.

Enligt honom finns det också andra omständigheter som talar för att skillnaderna kan vara underskattade, till exempel att statinbehandling och annan medicinsk förebyggande behandling var betydligt sämre i början av vår studieperiod då de flesta fick kirurgi.
– Sannolikt kommer ingen göra en randomiserad studie inom detta område eftersom typ 1-diabetes är en så pass ovanlig sjukdom. Vi tror att våra fynd är det närmaste sanningen man kan komma, säger Martin Holzmann.
Antalet flerkärlssjuka patienter med typ 1-diabetes som genomgick revaskularisering med endera metoden varierade under uppföljningsperioden från 97 till 185 årligen.

Resultaten visar att patienter som genomgått revaskularisering genom ballongvidgning hade 45 procent högre risk för att dö av hjärtsjukdom, och 47 procent högre risk att drabbas av hjärtinfarkt under den genomsnittliga 10-åriga uppföljningsperioden, jämfört med patienter som genomgått kranskärlskirurgi. De hade också en fem gånger högre risk för att behöva genomgå en andra ballongvidgning eller kranskärloperation.
– Resultaten talar för att kranskärlskirurgi bör vara förstahandsval även hos patienter med typ 1-diabetes som har två eller flera sjuka kranskärl, säger Martin Holzmann.
Forskarna kunde dock konstatera att andelen kranskärlsoperationer minskade dramatiskt under studieperioden. Åren 1995-2000  gjordes 58 procent av revaskulariseringarna vid typ 1-diabetes och minst två sjuka kranskärl genom kranskärlskirurgi och åren 2007-2013 var andelen kranskärlsoperationer endast 5 procent.
Martin Holzmann hoppas nu att den nya forskningen får genomslag i hälso- och sjukvården.
– En ballongutvidgning är enklare att genomföra och innebär ett mindre ingrepp på patienten, så det finns argument även för den metoden. Men både randomiserade studier och registerstudier har entydigt visat att kranskärlskirurgi är den bästa metoden för revaskularisering hos diabetespatienter med minst två sjuka kranskärl. Nu har vi fått ytterligare stöd för detta samt bekräftat att det gäller samtliga diabetespatienter, säger Martin Holzmann.
 
 
ABSTRACT
 
PCI Versus CABG in Patients With Type 1 Diabetes and Multivessel Disease
Thomas Nyström, MD, PHD,a,b Ulrik Sartipy, MD, PHD,c,d Stefan Franzén, PHD,e Björn Eliasson, MD, PHD,e
Soffia Gudbjörnsdottir, MD, PHD,e Mervete Miftaraj, MSC,e Bo Lagerqvist, MD, PHD,f Ann-Marie Svensson, PHD,e Martin J. Holzmann, MD, PHDg,h
 
BACKGROUND It is unknown if coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) may offer a survival benefit in patients with type 1 diabetes (T1D) in need of multivessel revascularization.
 
OBJECTIVES This study sought to determine if patients with T1D and multivessel disease may benefit from CABG compared with PCI.
 
METHODS In an observational cohort study, the authors included all patients with T1D who underwent a first multi-vessel revascularization in Sweden from 1995 to 2013. The authors used the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Thera-pies) register, the Swedish National Diabetes Register, and the Swedish National Patient Register to retrieve information about patient characteristics and outcomes. They estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) for all-cause and coronary heart disease mortality, myocardial infarction, repeat revasculari-zation, stroke, and heart failure using inverse probability of treatment weighting based on propensity scores.
 
RESULTS Intotal,683patientswhounderwentCABGand1,863patientswhounderwentPCIwereincluded.Duringamean
follow-up of 10.6 years, 53% of patients in the CABG group and 45% in the PCI group died. PCI, compared with CABG, was associated with a similar risk of all-cause mortality (HR: 1.14; 95% CI: 0.99 to 1.32), but higher risks of death from coronary heart disease (HR: 1.45; 95% CI: 1.21 to 1.74), myocardial infarction (HR: 1.47; 95% CI: 1.23 to 1.78), and repeat revascu-larization (HR: 5.64; 95% CI: 4.67 to 6.82). No differences in risks of stroke or heart failure were found.
 
CONCLUSIONS Notwithstanding the inclusion of patients with T1D who might not have been able to undergo CABG in the PCI group we found that PCI, compared with CABG, was associated with higher rates and risks of coronary heart disease mortality, myocardial infarction, and repeat revascularizations. Our findings indicate that CABG may be the preferred strategy in patients with T1D in need of multivessel revascularization. (J Am Coll Cardiol 2017;-:-–-) © 2017 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license http://creativecommons.org/licenses/by-nc-nd/4.0/
 
EDITORIAL
Type 1 Diabetes,
Coronary Disease Complexity, and
Optimal Revascularization Strategy*
Michael J. Domanski, MD, Michael E. Farkouh, MD, MS
 
Substantial clinical trial data have accumulated comparing coronary artery bypass grafting
(CABG) to percutaneous intervention (PCI) (1–4). These data consistently demonstrate the superiority of CABG over PCI in reducing long-term mortality and myocardial infarction (MI) in patients with stable but aggressive multivessel coronary artery disease (CAD). Aggressiveness of disease can be judged by extent/complexity (SYNTAX [Synergy Between PCI With Taxus and Cardiac Surgery] score) (1,2) or the presence of diabetes(3). CABG results in better outcomes than PCI in these patients, whether PCI is performed by balloon angioplasty alone, with bare-metal stents, or with drug-eluting stents.
Diabetes patients included in previous trials have primarily evaluated those with type 2 diabetes (T2DM). In this issue of the Journal, Nyström et al.(5) offers data specifically supporting CABG as the appropriate revascularization modality in patients with type 1 diabetes (T1DM).
Why is CABG the consistent “winner” in aggressive multivessel CAD regardless of the PCI procedure? Do we just need better stent platforms, or is there a fundamental difference in the physiological mecha-nism of benefit between these 2 revascularization procedures that favors CABG over PCI?
 
DISEASE COMPLEXITY
One consistent finding across studies comparing PCI with CABG is that the superiority of CABG is most pronounced when there is a greater degree of CAD complexity or disease aggressiveness.
The SYNTAX trial randomized 1,800 patients with 3-vessel or left main CAD to CABG or PCI (1,2). For the subgroup with 3-vessel disease, results after 5 years of follow-up showed that PCI resulted in a signifi-cantly higher rate of the composite endpoint of death, MI, or stroke (37.5% vs. 24.2%, respectively; p < 0.001) and long-term mortality in the 1,275 nondiabetic patients with multivessel CAD. In the SYNTAX trial, a scoring system (SYNTAX score) was used to categorize the extent and complexity of the CAD as low (#22), intermediate (23 to 32), or high ($33). The value of the SYNTAX score lies in its usefulness in predicting whether PCI or CABG is most likely to offer a better outcome for an individual patient. In fact, the 5-year results of the 3-vessel disease cohort in SYNTAX were dependent on lesion complexity as judged by the SYNTAX score, where patients with an intermediate or high ($33) scores had significantly greater adverse cardiovascular events with PCI than CABG (6). Subsequently, the SYNTAX 2 scoring system, which accounts for both anatomy and patient characteristics, was developed and validated (7).
 
DIABETES
There are inherent differences in the pathophysiology of T1DM and T2DM, but both are strongly linked to the development of CAD and increased cardiovascu-lar ischemic events (8).
The common link is that elevated plasma glucose results in an altered lipid profile, generation of
reactive oxygen species, and reduced nitric oxide availability, triggering a cascade of pro-inflammatory and -thrombotic biochemical events, resulting in atherosclerosis and increased risk of MI (9).
The FREEDOM (Comparison of Two Treatments for Multivessel Coronary Artery Disease in In-dividuals With Diabetes) (3) trial compared CABG to PCI with drug-eluting stents in patients with both diabetes (T1DM and T2DM) and multivessel CAD and showed that CABG is the revascularization procedure of choice in these patients. The benefit of CABG was driven by reductions in the rates of both MI (p < 0.001) and death from any cause (p ¼ 0.049).
 
SYNTHESIS
In patients with CAD and stable symptoms associated with diabetes or high SYNTAX score, the mechanisms of benefit of PCI and CABG are different, and this difference likely explains the superior results of CABG.
Arteries with 1 or more stenotic segments are known to have diffuse disease, including areas without significant lumen compromise. As a result, there is a nonzero probability of occlusion resulting in myocardial necrosis along the entire course of the artery; the risk at each point is a function of lesion characteristics (plaque structure and composition), the risk factor milieu (lipid level, smoking, and he-modynamics), individual predisposition (genetics), systemic disease (diabetes), and the presence of col-laterals. Underscoring this point, the published data show that a coronary occlusion causing myocardial infarction is frequently not located where a prior coronary angiogram demonstrated severe stenosis in the artery. The overall risk that an occlusive event will cause myocardial damage is the sum of the risk at each point along the entire artery.
PCI opening of flow-restricting lesions reduces symptoms by improving perfusion. Although the treated area may have a reduced probability of a subsequent occlusive event, no reduction in proba-bility of occlusion occurs in nonstented regions of the vessel—that is, in most of the artery. CABG also results in improved delivery of blood to myocardial regions whose flow is limited by vessel stenosis. However, when occlusion occurs proximal to the graft anastomosis to the native artery, regions distal to that occlusion are not rendered ischemic as they would have been following a PCI. So, a bypass graft that is in place distal to the site of an occlusive
event prevents infarction of regions distal to the site of the occlusive event. This means that CABG removes large segments of the artery that would have added to the total risk of necrosis by an occlusion.
Better stents alone cannot change the superiority of CABG compared with PCI for patients with aggressive CAD (diabetes or high SYNTAX score), because PCI addresses only a small portion of the coronary anatomy. This does not diminish the importance of continuing advances in stent technol-ogy, but rather, it puts into appropriate perspective what can be expected from these advances (10).
The study by Nyström et al. (5) examined all patients with T1DM and multivessel CAD who underwent a first multivessel revascularization in Sweden from 1995 to 2013, and found that results for CABG were superior to those for PCI with respect to coronary heart disease mortality, myocardial infarction, and heart failure.
The study has a number of strengths. No random-ized trial has compared revascularization strategies exclusively in patients with T1DM, so this paper provides information in an essentially data-free zone. However, the study also has several limitations. As an observational study, by its basic design it offers a chance of failure to balance recognized and unrec-ognized baseline differences between the study groups. Compared with the CABG group, patients in the PCI group were older; more often had cancer; and were more likely to have a history of stroke, heart failure, MI, or end-stage renal disease. In addition, the PCI group likely included patients who were not CABG candidates. In recent years, PCI has become the predominant approach, so that the control subjects in the study by Nyström et al. (5) are not really contemporaneous. This could also be explained by a number of mechanisms, including a better control of risk factors resulting in more focal CAD. This, however, is purely speculative.
The findings of this important study help to better inform practice, and should influence decision-making for revascularization in patients with T1DM.
 
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