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Adherence to Medications in Revascularized Patients
902
The American Journal of Cardiology (www.ajconline.org)
effect of iron deficiency at a range of haemoglobin and packed cell volumes. Br J Haematol 1986;63:369 –375. 7. Heusser F, Fahey JT, Lister G. Effect of hemoglobin concentration on critical cardiac output and oxygen transport. Am J Physiol 1989; 256:H527–H532. 8. Pearson TC, Grimes AJ, Slater NG, Wetherley-Mein G. Viscosity and iron deficiency in treated polycythaemia. Br J Haematol 1981; 49:123–127. doi:10.1016/j.amjcard.2011.06.027
Adherence to Medications in Revascularized Patients I read with great interest the recent report of Kulik et al1 on adherence to statin therapy in elderly patients after hospitalization for coronary revascularization. The investigators concluded that in patients receiving invasive coronary treatment, despite strong evidence supporting their use, statin adherence remains suboptimal. In another recent study addressing the adherence to medications,2 only 27% of patients who underwent coronary artery bypass grafting were treated with clopidogrel after hospital discharge, although the guidelines since 2004 have suggested that post–myocardial infarction patients take clopidogrel for 9 to 12 months after coronary artery bypass grafting.3–5 This had an impact on outcomes, as the clopidogrel-treated patients had a lower risk for the combined end point of death or recurrent myocardial infarction.2 In the study by Kulik et al,1 the prehospital use of clopidogrel in the coronary artery bypass grafting group was 19.5%, and postdischarge use was 9.3% (vs 22.1% in the medical therapy group after discharge). It is important to highlight this finding to focus on discharge medications of patients who undergo revascularization. Wassef Karrowni, MD Iowa City, Iowa
1. Kulik A, Shrank WH, Levin R, Choudhry NK. Adherence to statin therapy in elderly patients after hospitalization for coronary revascularization. Am J Cardiol 2011;107: 1409 –1414. 2. Sørensen R, Abildstrøm SZ, Hansen PR, Hvelplund A, Andersson C, Charlot M, Fosbøl EL, Køber L, Madsen JK, Gislason GH, Torp-Pedersen C. Efficacy of post-operative clopidogrel treatment in patients revascularized with coronary artery bypass grafting after myocardial infarction. J Am Coll Cardiol 2011;57:1202–1209.
3. Stein PD, Schunemann HJ, Dalen JE, Gutterman D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126(suppl):600 – 608. 4. Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, Nashef SA; EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 2008;34:73–92. 5. Becker RC, Meade TW, Berger PB, Ezekowitz M, O’Connor CM, Vorchheimer DA, Guyatt GH, Mark DB, Harrington RA; American College of Chest Physicians. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(suppl): 776 – 814. doi:10.1016/j.amjcard.2011.06.028
Authors’ Reply We appreciate Van De Bruaene et al’s interest in this topic and our report. The multiple relations that govern red cell production in cyanotic congenital heart disease are not well characterized in our opinion. Our own data are congruous with Van De Bruaene et al’s in showing that hematocrit is maintained in iron deficiency, whereas hemoglobin decreases. In other words, iron deficiency invokes production of smaller, hypochromatic cells, but red cell mass is unchanged, as are hematocrit and thus viscosity. We appreciate the authors’ point that because of this shift, theoretical viscosity for a given hemoglobin will be higher, although in practical terms, the same hemoglobin cannot be maintained if iron stores are low, and hence viscosity will likely be unchanged. The observation made by Van De Bruaene et al highlights the fact that cyanosis invokes a relative macrocytosis, as also shown by others.1 We fully agree with the authors’ point that hemoglobin and hematocrit have potential clinical impact, for different reasons, and should be considered separately. Craig S. Broberg, MD Portland, Oregon 25 June 2011
1. Kaemmerer H, Fratz S, Braun SL, Koelling K, Eicken A, Brodherr-Heberlein S, Pietrzik K, Hess J. Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease. Am J Cardiol 2004;94:825– 828. doi:10.1016/j.amjcard.2011.06.030
Immortal Person Time Bias in Pharmacoepidemiological Studies of Antihypertensive Drugs We read with interest the study of Huang et al1 examining the risk for cancer associated with the use of angiotensin II receptor blockers (ARBs) in a large observational cohort of Taiwanese subjects with incident hypertension. The study was motivated by a highly publicized meta-analysis of clinical trials that found a small but nominally significant increased risk for cancer in patients randomized to ARBs compared to those not randomized to ARBs (risk ratio 1.08, 95% confidence interval [CI] 1.01 to 1.15), driven largely by an excess risk for lung cancer (risk ratio 1.25, 95% CI 1.05 to 1.49).2 Contrary to this clinical trial meta-analysis, Huang et al1 report an impressive approximate 34% reduction in cancer risk associated with the use of ARBs. The reduction in risk was uniform across several co-morbid conditions and all major cancer sites, including lung cancer. The protective effect was substantially more pronounced in patients with ⬎1 year of exposure to ARBs (hazard ratio 0.50, 95% CI 0.46 to 0.53) compared to those with ⱕ1 year of exposure (hazard ratio 0.79, 95% CI 0.75 to 0.83). The strong duration-response relation suggests a causal association. Reports of an elevated cancer risk attributed to the use of various classes of antihypertensive drugs have transiently received widespread attention in the past. However, initial concerning reports have invariably been refuted through additional studies.3 ARBs appear to be following a similar course, with more recent expanded meta-analyses of clinical trials conducted by the United States Food and Drug Administration and others showing no excess risk for cancer in ARB users.4 – 6 Furthermore, a large Danish observational cohort study also detected no increased risk for cancer in ARB users.7 How then does one explain the extraordinary protective effects of ARBs on cancer risk observed by Huang et al1 in light of the totality of evidence coming from other studies? On the basis of the investigators’ declared analytic approach, we strongly suspect that the protective effect observed is merely a consequence of immortal person-time bias.8
The American Journal of Cardiology (www.ajconline.org)
effect of iron deficiency at a range of haemoglobin and packed cell volumes. Br J Haematol 1986;63:369 –375. 7. Heusser F, Fahey JT, Lister G. Effect of hemoglobin concentration on critical cardiac output and oxygen transport. Am J Physiol 1989; 256:H527–H532. 8. Pearson TC, Grimes AJ, Slater NG, Wetherley-Mein G. Viscosity and iron deficiency in treated polycythaemia. Br J Haematol 1981; 49:123–127. doi:10.1016/j.amjcard.2011.06.027
Adherence to Medications in Revascularized Patients I read with great interest the recent report of Kulik et al1 on adherence to statin therapy in elderly patients after hospitalization for coronary revascularization. The investigators concluded that in patients receiving invasive coronary treatment, despite strong evidence supporting their use, statin adherence remains suboptimal. In another recent study addressing the adherence to medications,2 only 27% of patients who underwent coronary artery bypass grafting were treated with clopidogrel after hospital discharge, although the guidelines since 2004 have suggested that post–myocardial infarction patients take clopidogrel for 9 to 12 months after coronary artery bypass grafting.3–5 This had an impact on outcomes, as the clopidogrel-treated patients had a lower risk for the combined end point of death or recurrent myocardial infarction.2 In the study by Kulik et al,1 the prehospital use of clopidogrel in the coronary artery bypass grafting group was 19.5%, and postdischarge use was 9.3% (vs 22.1% in the medical therapy group after discharge). It is important to highlight this finding to focus on discharge medications of patients who undergo revascularization. Wassef Karrowni, MD Iowa City, Iowa
1. Kulik A, Shrank WH, Levin R, Choudhry NK. Adherence to statin therapy in elderly patients after hospitalization for coronary revascularization. Am J Cardiol 2011;107: 1409 –1414. 2. Sørensen R, Abildstrøm SZ, Hansen PR, Hvelplund A, Andersson C, Charlot M, Fosbøl EL, Køber L, Madsen JK, Gislason GH, Torp-Pedersen C. Efficacy of post-operative clopidogrel treatment in patients revascularized with coronary artery bypass grafting after myocardial infarction. J Am Coll Cardiol 2011;57:1202–1209.
3. Stein PD, Schunemann HJ, Dalen JE, Gutterman D. Antithrombotic therapy in patients with saphenous vein and internal mammary artery bypass grafts: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126(suppl):600 – 608. 4. Dunning J, Versteegh M, Fabbri A, Pavie A, Kolh P, Lockowandt U, Nashef SA; EACTS Audit and Guidelines Committee. Guideline on antiplatelet and anticoagulation management in cardiac surgery. Eur J Cardiothorac Surg 2008;34:73–92. 5. Becker RC, Meade TW, Berger PB, Ezekowitz M, O’Connor CM, Vorchheimer DA, Guyatt GH, Mark DB, Harrington RA; American College of Chest Physicians. The primary and secondary prevention of coronary artery disease: American College of Chest Physicians evidence-based clinical practice guidelines (8th edition). Chest 2008;133(suppl): 776 – 814. doi:10.1016/j.amjcard.2011.06.028
Authors’ Reply We appreciate Van De Bruaene et al’s interest in this topic and our report. The multiple relations that govern red cell production in cyanotic congenital heart disease are not well characterized in our opinion. Our own data are congruous with Van De Bruaene et al’s in showing that hematocrit is maintained in iron deficiency, whereas hemoglobin decreases. In other words, iron deficiency invokes production of smaller, hypochromatic cells, but red cell mass is unchanged, as are hematocrit and thus viscosity. We appreciate the authors’ point that because of this shift, theoretical viscosity for a given hemoglobin will be higher, although in practical terms, the same hemoglobin cannot be maintained if iron stores are low, and hence viscosity will likely be unchanged. The observation made by Van De Bruaene et al highlights the fact that cyanosis invokes a relative macrocytosis, as also shown by others.1 We fully agree with the authors’ point that hemoglobin and hematocrit have potential clinical impact, for different reasons, and should be considered separately. Craig S. Broberg, MD Portland, Oregon 25 June 2011
1. Kaemmerer H, Fratz S, Braun SL, Koelling K, Eicken A, Brodherr-Heberlein S, Pietrzik K, Hess J. Erythrocyte indexes, iron metabolism, and hyperhomocysteinemia in adults with cyanotic congenital cardiac disease. Am J Cardiol 2004;94:825– 828. doi:10.1016/j.amjcard.2011.06.030
Immortal Person Time Bias in Pharmacoepidemiological Studies of Antihypertensive Drugs We read with interest the study of Huang et al1 examining the risk for cancer associated with the use of angiotensin II receptor blockers (ARBs) in a large observational cohort of Taiwanese subjects with incident hypertension. The study was motivated by a highly publicized meta-analysis of clinical trials that found a small but nominally significant increased risk for cancer in patients randomized to ARBs compared to those not randomized to ARBs (risk ratio 1.08, 95% confidence interval [CI] 1.01 to 1.15), driven largely by an excess risk for lung cancer (risk ratio 1.25, 95% CI 1.05 to 1.49).2 Contrary to this clinical trial meta-analysis, Huang et al1 report an impressive approximate 34% reduction in cancer risk associated with the use of ARBs. The reduction in risk was uniform across several co-morbid conditions and all major cancer sites, including lung cancer. The protective effect was substantially more pronounced in patients with ⬎1 year of exposure to ARBs (hazard ratio 0.50, 95% CI 0.46 to 0.53) compared to those with ⱕ1 year of exposure (hazard ratio 0.79, 95% CI 0.75 to 0.83). The strong duration-response relation suggests a causal association. Reports of an elevated cancer risk attributed to the use of various classes of antihypertensive drugs have transiently received widespread attention in the past. However, initial concerning reports have invariably been refuted through additional studies.3 ARBs appear to be following a similar course, with more recent expanded meta-analyses of clinical trials conducted by the United States Food and Drug Administration and others showing no excess risk for cancer in ARB users.4 – 6 Furthermore, a large Danish observational cohort study also detected no increased risk for cancer in ARB users.7 How then does one explain the extraordinary protective effects of ARBs on cancer risk observed by Huang et al1 in light of the totality of evidence coming from other studies? On the basis of the investigators’ declared analytic approach, we strongly suspect that the protective effect observed is merely a consequence of immortal person-time bias.8