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Reviews |
Department of Clinical Biochemistry (Vascular Disease Prevention Clinics) and Academic Department of Surgery, Royal Free Hospital, Pond Street, London NW3 2QG, UK
Received 10 October 2007; received in revised form 12 December 2007; accepted 12 December 2007.
* Corresponding author. Tel.: +44 20 7830 2258; fax: +44 20 7830 2235. (Email: paraskevask{at}hotmail.com).
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Abstract |
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 Top Abstract 1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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Key Words: Statins • Coronary artery bypass grafting • Cardiac transplantation • Valve surgery • Cardiac surgery • Thoracic aortic aneurysm
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1. Introduction |
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TopAbstract1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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Statins are safe drugs with very few adverse effects described; their most frequent side-effects (liver failure and rhabdomyolysis) occur at a rate of only one case per 1,000,000 person–years [22,23].
This review discusses the multiple beneficial effects of statins in cardiothoracic surgery.
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2. Literature search methods |
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TopAbstract1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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3. Literature search results |
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TopAbstract1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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The effects of statins on cardiothoracic surgical procedures are briefly presented.
3.1 Statins and CABG
Early studies showed that atherosclerosis frequently develops in saphenous vein coronary bypass grafts leading to occlusion rates as high as 40% at 10–12 years following CABG surgery [24,25]. An observational study following up 1041 post-CABG patients for 20 years showed that one in five patients underwent repeat CABG and another 7% had percutaneous transluminal coronary angioplasty during this time period [26]. These progressive atherosclerotic obstructive changes are especially common in patients with hyperlipidemia [27–30]. The key role of managing hyperlipidemia in these patients was demonstrated in the post-CABG trial [31]. Compared with moderate lipid-lowering treatment with lovastatin (target low-density lipoprotein cholesterol (LDL-C): 132–136 mg/dl), aggressive lovastatin treatment aiming at target LDL-C levels <100 mg/dl resulted in a reduced percentage of grafts per patient with angiographically detected atherosclerosis progression after a mean follow-up of 4.3 years (39% vs 27%, respectively; p
< 0.001). Similar results were reported regarding the mean percentage of grafts per patient with occlusion or new lesions (Table 1
) [31]. The post-CABG trial was designed to have adequate power to detect treatment-related differences in angiographic characteristics but not in clinical events. As a result, a reduction in the number of clinical events was not seen [31]. Nevertheless, a 29% lower rate of revascularization procedures was observed in the aggressive compared with the moderate treatment group (p
= 0.03) [31].
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Following the post-CABG trial, several other studies on patients undergoing CABG showed that statin treatment is beneficial in these patients with respect to the incidence of postoperative adverse cardiovascular outcomes (unstable angina, MI, arrhythmia, stroke and cardiac death) (Table 1). The possible mechanisms through which statins exert their beneficial actions in CABG are reviewed elsewhere [33–35]. Briefly, these include reduction of inflammation and oxidative stress, improvement of vascular endothelial function and management of postoperative hyperlipidemia/dyslipidemia [33–35]. Lipid-lowering in post-CABG patients is crucial; hyperlipidemia is responsible for the development of atherosclerotic changes in vein grafts eventually leading to graft occlusion [34,35].
Preoperative statin therapy in CABG patients improves postoperative myocardial perfusion of bypassed areas [36]. It also significantly reduces cytokine release (such as interleukin (IL)-6 [37–39] and IL-8 [37]) and neutrophil adhesion to the venous endothelium via a nitric oxide-mediated mechanism. Preoperative statin treatment is also associated with improved perioperative mortality rates [40–43] and reduced risk of postoperative thrombocytosis and thrombotic complications [44]. Postoperative thrombocytosis occurs in 20–30% of the patients undergoing CABG and it is associated with an increase in late thrombotic complications [45]. Furthermore, pre-CABG statin use is associated with a 33% reduction in the odds of developing a postoperative infection and a 20% reduction in the odds of requiring a prolonged postprocedural hospitalization [46]. Another beneficial action of statins in CABG patients is stroke prevention, which is one of the most serious complications of this procedure [47]; a recent prospective study showed that, compared with non-use, statin treatment for at least 4 weeks prior to surgery was significantly and independently associated with a lower risk of perioperative cerebrovascular events (odds ratio (OR) 0.26; 95% confidence interval (CI) 0.06–086; p = 0.027) [47].
Acute renal failure occurs in 1–5% of the patients following CABG surgery [48–50]. It is associated with mortality rates as high as 60% [48,49] and substantial increases in the lengths of intensive care and hospital stay [48–50]. A large, multi-center trial including 19,625 patients undergoing isolated CABG surgery showed that patients with preoperative non-dialysis-dependent renal dysfunction had significantly higher in-hospital mortality (adjusted OR 3.0; p < 0.001), stroke (adjusted OR 2.0; p = 0.33), atrial arrhythmia (adjusted OR 1.5, p = 0.003), prolonged ventilation (adjusted OR 2.1; p < 0.001), postoperative hospital stay >6 days (adjusted OR 2.6; p < 0.001) and follow-up mortality rates (adjusted OR 2.7; p < 0.001) [51]. A retrospective cohort study including 1802 CABG patients suggested that preoperative statin therapy might be renoprotective in patients undergoing CABG [52]. By multivariate analysis, preoperative statin use was associated with an almost 50% lower incidence of new postoperative renal insufficiency (OR 0.54, 95% CI 0.18–0.82; p = 0.047) [52].
Statins exert several beneficial actions on saphenous venous bypass graft patency rates. A 4-year prospective study with a median follow-up of 32 months (mean: 38.54 ± 0.54 months) investigated predictors of symptom recurrence (recurrent angina, MI and congestive heart failure) and adverse cardiac events (MI, coronary reintervention and any cardiac-related mortality including sudden cardiac death) in 591 patients undergoing CABG [53]. Following the procedure, statins were used in 391 patients (66.1%). Postoperative statin use was associated with both decreased symptom recurrence (hazard ratio (HR) 0.157, 95% CI 0.075–0.330; p < 0.0001) and adverse cardiac events (HR 0.178, 95% CI 0.076–0.418; p < 0.0001)) [53]. Similar results were also reported in other studies [31,54–58]; statins improve endothelial cell function and inhibit smooth muscle cell proliferation in human saphenous veins thus effectively decreasing progression of atherosclerosis in the vein grafts used in CABG [31,54–58].
An interesting study evaluated the predictive role of preoperative C-reactive protein (CRP) levels in the long-term outcome of 843 patients undergoing CABG [59]. Among operative survivors (753 patients with low CRP (<1.0 mg/dl) and 87 with high CRP (
1.0 mg/dl)), patients in the low CRP group had significantly better 12-year overall survival rate (74.1% vs 63.0%; p
= 0.004) and survival freedom from fatal cardiac events (86.7% vs 78.1%; p
= 0.008). In multivariate analysis, CRP 1.0 mg/dl was an independent predictor of late all-cause mortality (risk ratio 1.60, 95% CI 1.09–2.35; p
= 0.017) [59]. These results were verified by an independent group [60]; high preprocedural CRP levels were associated with an almost 6-fold increase in 9-month mortality rates in 108 patients with left main coronary artery stenosis treated with CABG (HR 5.86, 95% CI 1.71–20.03; p
= 0.005) [60]. Statins effectively reduce circulating CRP levels [61–63]. Therefore, their use may be associated with a beneficial effect on long-term survival rates in post-CABG patients.
Statins are also protective against de novo atrial fibrillation developing following CABG [64–67]. Post-CABG atrial fibrillation is a frequent complication occurring in approximately one third of male patients and 40% of female patients [68]. International guidelines on the management of atrial fibrillation after cardiac and thoracic surgery were recently reported [69]. Two earlier meta-analyses showed that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers effectively prevent the development of new onset atrial fibrillation in patients with cardiovascular diseases [70,71]. Nevertheless, a cohort evaluation study showed that preoperative use of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers was associated with a non-significant 29% reduction in postoperative atrial fibrillation (adjusted OR 0.71, 95% CI 0.42–1.20, p = 0.20) [72]. Therefore, their use for the management of post-CABG atrial fibrillation has limitations. Two studies showed that de novo atrial fibrillation following CABG is associated with several inflammation-associated parameters and inflammatory cytokines [73,74]. It was thus hypothesized that statins, by reducing postoperative inflammatory response, could be beneficial for these patients [73]. It remains to be determined whether statin treatment should play a role in the therapeutic approach of these patients.
An important issue that is often neglected is continuation of preoperative statin therapy following CABG surgery. It was recently demonstrated that post-CABG discontinuation of statin therapy in patients who were on statins preoperatively is associated with an increase in late (>4 days postoperatively) cardiac and all-cause mortality compared with continuous statin use following the procedure (2.64% vs 0.60%, respectively; adjusted OR 2.64; 95% CI 1.32–5.26; p < 0.01) [40]. This correlation was seen even when controlling for the postoperative discontinuation of other medications (e.g. aspirin, beta-blocker, or angiotensin-converting enzyme inhibitors) [40]. Discontinuation of statin therapy after surgery was also independently associated with a significant increase in late cardiac mortality compared with continuous postoperative statin use (1.91% vs 0.45%, respectively; adjusted OR 2.95; 95% CI 1.31–6.66; p < 0.01) [40]. It is, therefore, crucial not to discontinue statin therapy postoperatively in these patients.
A different opinion has also been reported. In a single-center retrospective study, 1706 patients undergoing isolated CABG or CABG combined with heart valve surgery were classified according to preoperative statin use (1075 statins users vs 631 non-users) [75]. An analysis according to preoperative statin use showed that, compared with non-users, statin users were more likely to undergo non-urgent in-house surgery (54.2% vs 70.8%, respectively; p = 0.0001) and have an ejection fraction <40% (23.0% vs 14.8%, respectively; p = 0.0001). The end-points of interest analyzed were in-hospital mortality, intra- or postoperative intra-aortic balloon pump use, perioperative MI, stroke, prolonged (>24 h) ventilation and a composite outcome defined as a combination of 2 or more of the above. The results of this analysis showed that preoperative statin use was not associated with a reduction of in-hospital mortality (OR 1.0, 95% CI 0.6–1.5, p = 0.85), the composite outcome (OR 1.1, 95% CI 0.8–1.4, p = 0.69) or any of the outcomes of interest [75]. Until now, these results have not been verified by other independent studies.
3.2 Statins and valve surgery
It was suggested that statins might reduce the progression of calcific aortic valve stenosis [76–79]. According to one theory, aortic stenosis is the product of an active inflammatory process, which shares many similarities with atherosclerosis (e.g. lipoprotein accumulation) [76,80,81]. An additional finding supporting this theory is that aortic stenosis progresses faster in patients with hypercholesterolemia [78]. As statins are indicated both in the management of hypercholesterolemia [82,83] and atherosclerosis [84,85], it is possible that these agents comprise an effective way to retard the progression of aortic stenosis.
Statins have also been reported to reduce aortic valve calcium accumulation [86,87], as well as the progression of biologic prosthetic aortic valve degeneration [88,89]. The explanation for these results was provided by a retrospective cohort study; by stepwise multiple regression analysis, it was shown that hypercholesterolemia was an independent predictor for bioprosthetic aortic or mitral valve calcification (p = 0.02) [90]. These effects hold considerable implications both in the conservative and the surgical management of patients with aortic valve stenosis. The extent of aortic valve calcification is a strong predictor of aortic valve stenosis [87]. Thus, by retarding this process, the rates of progression of aortic valve stenosis are reduced. Furthermore, an effect of statins on the progression of biologic prosthetic aortic valve degeneration [88,89] could potentially influence the type of aortic valve prosthesis selected in patients requiring aortic valve replacement.
It was proposed that statins might have a role in the management of patients with congenital bicuspid aortic valve malformations [90]. These patients are at a higher risk of developing aortic stenosis, aortic root dilation, aortic regurgitation, aortic aneurysm, aortic dissection and infective endocarditis. This is done via two different mechanisms: (i) by reducing the progression of aortic stenosis and aortic valve calcification [76–79,88,89]; and (ii) by limiting aortic dilatation through inhibition of matrix metalloproteinases (MMPs) [91–93] and improvement of endothelial function [94,95].
Whether statin therapy has an effect on long-term morbidity and mortality rates following valve surgery has not been investigated so far. A recent systematic review including 28 studies and a total of 106,660 patients did not identify statin non-use as a predictor of early or late mortality following aortic valve replacement [96]. Nevertheless, statins may improve some of the predictors of mortality identified, such as renal dysfunction [97,98] and coronary artery disease [11–13,99,100]. Thus, it could be hypothesized that statins potentially influence mortality rates following valve surgery in an indirect way.
Two prospective, randomized, multi center, double-blind, placebo-controlled trials, the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial in Canada [101] and the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) Study in Europe [102] are currently under way. The ASTRONOMER trial aims to determine the effect of rosuvastatin 40 mg/day versus placebo on the rate of cardiac death and aortic valve replacement in patients with mild to moderate aortic stenosis. The results of this trial, which will be available at the end of 2008, will clarify the role of statin therapy in the management of aortic stenosis [101]. The SEAS Study investigates the effect of lipid-lowering with a combination of ezetimibe 10 mg/day and simvastatin 40 mg/day in patients with asymptomatic aortic stenosis with peak transvalvular jet velocity 2.5–4.0 m/s. The results of the SEAS Study will help determine the prognostic value of aggressive lipid-lowering treatment in patients with asymptomatic aortic stenosis [102].
3.3 Statins and cardiac transplantation
Transplant coronary artery disease (cardiac allograft vasculopathy) remains the leading cause of death or retransplantation in cardiac transplant recipients up to 5 years post-transplant, accounting for nearly 30% of deaths [103,104]. It is characterized by a diffuse proliferative vasculopathy limited to the allograft coronary arteries and is associated with the development of MI, ventricular failure, malignant arrhythmias and sudden death [103–106]. Besides antiproliferative and immunosuppressive agents (such as ciclosporin, sirolimus and everolimus), routine statin use in heart transplant patients for the management of cardiac allograft vasculopathy has been advocated [107,108].
Early in vitro studies with HMG-CoA reductase inhibitors showed that these agents suppress natural killer cells [109,110]. Interpretation of this finding suggested an immunomodulatory role for statins in the management of acute rejection and coronary vasculopathy [111]. These preliminary results were also verified in animals; statins were shown to affect coronary vasculopathy by a mechanism independent of cholesterol lowering [112,113].
Based on the positive results of in vitro and animal studies, a similar effect on human cardiac transplantations was hypothesized. An early, randomized, placebo-controlled trial showed that, compared with placebo, 12-month treatment with pravastatin 40 mg/day was associated with improved 1-year survival rates, as well as reduced incidence of coronary vasculopathy and cardiac rejection rates [114]. Additionally, there was significantly lower natural killer cell cytotoxicity in the pravastatin compared with the placebo group (9.8% vs 22% specific lysis, respectively; p = 0.014) [114]. The results of several other trials support a role for statins in cardiac transplantation (Table 2 ).
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, IL-6 and soluble IL-2R levels) [63,124,125]. Statins also inhibit excessive expression of monocyte tissue factor and reduce the persistent hypercoagulability state seen in cardiac transplant recipients [126]. Statin use in cardiac transplant recipients is associated with improved cardiac ejection fraction [127], as well as a reduced risk for chronic renal failure, which is a relative common condition in heart transplantation associated with substantial mortality [128]. These multiple beneficial actions render statins a valuable tool in the postoperative management of heart transplant recipients. Several in vitro and animal reports have implicated MMPs in the pathogenesis of coronary vasculopathy and acute and chronic cardiac allograft rejection [129–132]. Statins effectively suppress production of MMPs in several tissues and organs [92,133–135]. Through their effect on MMPs, statins may reduce coronary vasculopathy and cardiac rejection rates.
An important issue in heart transplantation is the extent of coronary atherosclerosis of the donor heart [136]. Statins have been reported to cause regression of coronary atherosclerosis [137,138]. A recent animal study also showed that statins attenuate transplant-associated coronary arterial intima hyperplasia and arteriosclerosis in a murine model of cardiac transplantation [139]. Moreover, statin therapy initiated early after heart transplantation leads to better short- and long-term survival rates and a significantly lower incidence of transplant vasculopathy without impairment of organ function or severe adverse effects [140–144]. An economic analysis showed that statin therapy after heart transplantation offers a significant survival benefit and a lower incidence of graft vessel disease in a cost-effective way [145]. These findings hold implications for an important role of statin therapy in heart transplantation.
Another important issue is post-transplant hyperlipidemia/dyslipidemia [146]. The risk of developing hyperlipidemia/dyslipidemia following orthotopic heart transplantation is estimated to range between 50% and 80% [147,148]. The association between hyperlipidemia/dyslipidemia and the development of coronary allograft vasculopathy is well established [148–150]. Statins successfully reduce post-transplant hyperlipidemia/dyslipidemia, coronary allograft vasculopathy and mortality rates in both pediatric [151–154] and adult heart transplant patients [140,141,144,155–160]. The results from randomized trials suggest that the optimal time for initiation of statin therapy is early (<3 years) after cardiac transplantation [140,141,144,155–160]. A possible explanation for this finding is that the immunomodulatory effects of statins are most important in the early post-transplant period perhaps preventing endothelial dysfunction and the cascade that leads to allograft vasculopathy [156–158].
A meta-analysis of the effect of statin therapy initiated within 3 months after cardiac transplantation in patients aged >18 years followed up for 1 year showed that statin use was associated with a significant reduction in mortality in cardiac transplant patients (relative risk 0.31; 95% CI 0.13–0.7; p
= 0.006) [142]. It was demonstrated that statins are associated with one life saved for every 8.5 heart transplant recipients treated for 1 year. A different interpretation of the results showed that routine statin treatment in cardiac transplant patients might have the potential to save 471 lives each year among the 4000 heart transplantation operations performed worldwide [142]. Besides being effective and safe [141,142,144,151–163], statin use in cardiac transplant patients is also cost-effective [145]. Despite this, there is evidence suggesting that hyperlipidemias/dyslipidemias are suboptimally managed in many cardiac transplant patients [155].
Future trials are expected to define the exact role of statin therapy in heart transplantation. Encouraging results emerged recently from a cardiac transplantation animal model [164]; soluble IL-1 type-2 receptor gene transfer was demonstrated to attenuate cardiac allograft rejection in a rat model [164]. The authors concluded that IL-1 inhibition might prove useful as an adjuvant therapy in heart transplantation [164]. Statins were shown to be potent inhibitors of several members of the IL family in heart transplantation [63,124] and CABG studies [38–40]. Therefore, a role for these agents in cardiac transplantation should be expected.
3.4 Statins and lung transplantation
The results from preliminary studies suggest that statins play an important role in lung transplantation. Pravastatin was shown to prolong graft survival in an allogeneic rat model of orthotopic lung transplantation [165]. It was supported that the mechanism via which statins exert their beneficial effect may involve inhibition of major histocompatibility complex (MHC) class II molecules [165].
A retrospective study consisting of 200 consecutive patients who survived >30 days after pulmonary transplantation compared the effects of statin use versus non-use on lung transplantation (39 statin users vs 161 non-users) [166]. Compared with controls, statin users had a lower incidence of acute rejection rates, as defined by acute cellular rejection established from lung biopsies (25.6% vs 15.1%, respectively; p < 0.01). Furthermore, patients on statins had lower incidence of chronic (1 year) rejection as determined by signs of obliterative bronchiolitis in lung biopsy (37% vs 0%, respectively; p < 0.01) and improved 6-year survival rates (91% vs 54%, respectively; p = 0.002). A limitation of this retrospective study is that there was no randomization; statins were prescribed to lung transplant recipients solely for the treatment of hypercholesterolemia (>240 mg/dl) refractory to dietary modification [166]. As a result, the results produced are liable to inherent limitations and/or unrecognised biases. A prospective observational study on 64 patients (37 elective cardiac and 27 vascular surgery patients of whom 68% and 44%, respectively had received prior statin therapy) did not reveal significant differences caused by statins in the pulmonary capillary permeability of these patients [167]. Preoperative statin therapy neither had an adverse effect on mildly increased pulmonary capillary permeability nor did it ameliorate increased capillary permeability [167].
Following lung transplantation, lung ischemia–reperfusion injury occurs which is associated with an increase in vascular permeability and manifests itself clinically as pulmonary edema [168]. During the early phase of the ischemia–reperfusion injury, there is increased free radical production, which is secondary to increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in alveolar macrophages [168–170]. Statins were shown to inhibit NADPH oxidase in vitro resulting in decreased production of reactive oxygen intermediates [169,170]. An animal study verified the positive results of in vitro studies [171]; statin pretreatment prior to induction of experimental lung ischemia–reperfusion injury lead to a reduction in lung vascular permeability by 71% (p = 0.001). It was concluded that statin pretreatment of lung transplant recipients to ameliorate reperfusion injury appears to be a promising novel protective strategy [171].
The results of these preliminary studies need to be verified in prospective randomized trials before solid conclusions are drawn regarding the efficacy of statin treatment in lung transplantation.
3.5 Statins and thoracic aortic aneurysms
It was shown that oxidative stress plays a pivotal role in the pathogenesis of thoracic aortic aneurysms [91]. More specifically, the generation of reactive oxygen species was demonstrated to be markedly increased in the aneurysmal aorta compared with non-aneurysmal controls [91]. Reactive oxygen species activate MMPs [172]. An imbalance between MMPs and their inhibitors is crucial in the remodelling of the aortic wall and the pathogenesis of AAAs [173–176]. Activation of MMPs contributes to destructive remodelling of the aortic wall and the development of thoracic aortic aneurysms [91]. As earlier mentioned, statins effectively suppress production of MMPs [133–135]. It can, therefore, be assumed that these agents may reduce expansion rates of thoracic aortic aneurysms. A beneficial effect of statins on abdominal aortic aneurysms has already been described [177]; statins were demonstrated to reduce abdominal aortic aneurysm growth rates in both animal [93,178] and human studies [179,180].
Future trials may also show an effect of statin treatment on long-term morbidity and mortality rates in patients undergoing thoracic aortic aneurysm repair. In a long-term (4.7 years) follow-up study of patients who had undergone successful abdominal aortic aneurysm surgery it was demonstrated that, compared with non-users, statin users had significantly reduced all-cause (50% vs 18%; or 178 of 356 vs 27 of 154 patients, respectively; p < 0.001) and cardiovascular (34% vs 11%; or 122 of 356 vs 17 of 154 patients; p < 0.001) mortality rates [181]. After adjusting for clinical risk factors and beta-blocker use, the association between statin use and reduced all-cause (HR 0.4, 95% CI 0.3–0.6; p < 0.001) and cardiovascular (HR = 0.3, 95% CI 0.2–0.6; p < 0.001) mortality persisted [181]. Statins also reduce cardiac events in patients undergoing non-cardiac vascular surgery [182,183] and improve perioperative morbidity and mortality rates in these patients [184]. Up to now, there have not been any similar reports on patients undergoing thoracic aortic aneurysm repair. Nevertheless, extrapolating from the results of the above studies [181–184], similar effects for statins on thoracic aortic aneurysms should be expected.
3.6 Statins and thoracic surgery
Postoperative atrial fibrillation/flutter (and, generally, atrial arrhythmias) are seen in more than one in five elderly patients undergoing non-cardiac thoracic surgery [185]. These incidents are associated with a prolonged hospitalization and increased associated costs [185]. Consequently, the establishment of measures to decrease the incidence of postoperative atrial arrhythmias following non-cardiac thoracic surgery holds implications for better patient management, decreased morbidity and mortality rates and reduction of the length (and cost) of hospital stay.
A total of 131 patients scheduled to undergo pulmonary lobectomy (n = 117), pneumonectomy (n = 5) or esophagectomy (n = 9) were enrolled in a prospective study investigating the role of preoperative statin therapy in the management of atrial fibrillation following non-cardiac thoracic surgery [186]. The occurrence of atrial fibrillation in statin users was significantly lower compared with non-users (4 of 28 vs 27 of 93 patients, or 11% vs 29%, respectively, p = 0.025). After stepwise logistic regression, statin use was associated with a >three-fold decrease in the odds of developing atrial fibrillation (OR 0.26, 95% CI 0.08–0.82; p = 0.022). The protective effect of statins was independent of CRP levels [186]. Interpretation of these results showed that levels of CRP and inflammatory markers (e.g. IL–6) were not accurate predictors of the postoperative occurrence of atrial fibrillation [186].
Additionally, oxidative stress is prominent during pulmonary lobectomy [187]. The degree of oxidative stress generated is associated with the duration of the procedure (p < 0.001) [187]. Moreover, severe oxidative stress is an independent predictor of postoperative cardiopulmonary complications, namely acute respiratory failure, cardiac arrhythmias and pulmonary hypertension (for all, p < 0.05) [187]. Statins reduce oxidative stress via several mechanisms [188–191]. In addition to direct antioxidant effects, statins reduce circulating oxidized LDL particles and inhibit their uptake by macrophages. Furthermore, they inhibit oxidant enzymes activity (such as that of reduced NADPH oxidase and myeloperoxidase) and up-regulate the activity of antioxidant enzymes (such as catalase and paraoxonase). They also reduce endothelial dysfunction mainly by their ability to enhance endothelial nitric oxide bioavailability, which is achieved by several mechanisms [188–191]. It should be expected that the net result will be reduction of oxidative stress and, consequently, postoperative complications.
3.7 Evidence for patient undertreatment with respect to statins
Several studies have demonstrated that a considerable proportion of cardiovascular patients are undertreated with respect to statins [192–198]. As a result of the suboptimal statin treatment in this high-risk population, cardiovascular event and mortality rates remain high [192–198]. This also applies to CABG surgery patients. A recent study showed that approximately 25% of patients referred for elective CABG are not on statin treatment [199]; even among statin users, the majority of patients were prescribed very low dosages, which were not adequate to achieve LDL–C targets [199]. Several other studies have shown that one in two patients do not receive statin therapy at discharge following CABG surgery [200–202]. Risk management in these patients should be improved as it has been demonstrated that even a modest increase in statin prescribing rates could lead to substantial reduction of cardiovascular events and improvement of morbidity and mortality rates [198].
Statins are well-tolerated agents with few adverse effects [22,23,203]. In patients receiving chronic statin treatment, regular monitoring of liver function tests is advised. Detection of an abnormal elevation of liver enzymes is an indication that the statin dose should be decreased [22,23,203]. If the plasma hepatic enzyme levels remain elevated despite adaptation of the prescribed dose, it may be necessary to stop the statin treatment [22,23,203].
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4. Conclusions |
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TopAbstract1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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In addition to these effects, statins decrease cardiac allograft vasculopathy and cardiac rejection rates in cardiac transplant patients. Although no definite conclusions can be drawn yet, current evidence implies that statin therapy is beneficial in patients undergoing heart valve surgery, lung transplantation, pulmonary resection and thoracic aortic aneurysm repair.
Cardiothoracic surgical patients are undertreated with respect to statins. As a result, cardiovascular event and mortality rates remain high. Improvement of statin prescription rates in this high-risk group would have important consequences on cardiovascular morbidity and mortality rates.
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TopAbstract1. Introduction2. Literature search methods3. Literature search results4. ConclusionsReferences |
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