- Email: [email protected]
Effects of long-term use of cardiovascular drugs
Correspondence
Millions of people are prescribed drugs to prevent and treat cardiovascular disease for decades, even though the long-term safety and efficacy of these drugs are unknown. Introduction of the polypill (typically containing aspirin, statin, beta-blocker, and angiotensin-converting-enzyme inhibitor) without evidence of its long-term effects provides an additional challenge. This concern is particularly relevant to beta-blockers. DGJ experienced two potentially fatal events almost certainly due to the drug. After the first event, he was identified to have hypotension on exercise; after the second, he was diagnosed with extreme bradycardia due to sinoatrial block. Both abnormalities ceased when beta-blockers were stopped. If he had died, his death would not have been attributed to the drug. Should beta-blockers be prescribed in the long term in the absence of angina symptoms or heart failure? Some publications have questioned the effectiveness of beta-blockers in preventing death and recurrent infarction.1,2 Meta-analyses suggest no beneficial effect of beta-blockers on mortality in chronic stable angina, 3,4 and a review 2 into their use after myocardial infarction questioned their value after the first year or so, at least in those with preserved ventricular function. The effectiveness and safety of drugs might change with age of the individual. There might be other drugs, besides beta-blockers, which although beneficial in the short term, might have harmful effects in the long term. For instance, the long-term use of high-dose statins over decades might not be warranted. The potential harm caused by long-term use of treatments in elderly people should be a priority for organisations responsible for drug safety—eg, regulatory agencies www.thelancet.com Vol 385 January 24, 2015
such as the US Food and Drug Administration and the European Medicines Agency—but does not seem to be one. Post-approval long-term studies should be done. Randomised trials of withdrawal versus continuation of drugs (eg, beta-blockers) are also needed.5 We need reliable evidence to establish when to stop long-term use of cardiovascular drugs that are effective and safe in the short term. Improved data for whether elderly patients might be harmed by continuance of drug treatments prescribed many years earlier is needed.6 We declare no competing interests.
Desmond G Julian, *Stuart J Pocock [email protected] Netherhall Gardens, London NW3 5RN, UK (DGJ); and London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK (SJP) 1
2
3
4
5
6
Bangalore S, Steg PG, Deedwania P, et al. Beta-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 2012; 308: 1340–49. Kezerashvile A, Marzo K, De Leon J. Beta-blocker use after acute myocardial infarction in the patient with normal systolic function: when is it “ok” to discontinue? Curr Cardiol Rev 2012; 8: 77–84. Huang HL, Fox KA. The impact of beta-blockers on mortality in stable angina: a meta-analysis. Scott Med J 2012; 57: 69–75. Shu de F, Dong BR, Lin XF, Wu TX, Liu GJ. Long-term beta blockers for stable anginas: systematic review and meta-analysis. Eur J Prev Cardiol 2012; 19: 330–41. Pocock SJ, Gersh BJ. Do current clinical trials meet society’s needs? A critical review of recent evidence. JACC 2014; 64: 1615–28. Gnjidic D, Le Couteur DG, Hilmer SN. Discontinuing drug treatments: we need better evidence to guide deprescribing. BMJ 2014; 349: g7013.
stenting. By contrast, a strategy of prolongation of DAPT for up to 2 years might be harmful because of increased major or minor bleedings in the continuation group.2 However, previous data could show that in a low-risk population, like the one included in this study, DAPT duration of only 6 months after second-generation DES implantation is not inferior compared with 12 months of DAPT in terms of the incidence of cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, and major bleedings at 12 months.3 Even a shorter duration of DAPT (3 months) in patients with stable coronary artery disease or low-risk acute coronary syndrome given second-generation DES was not inferior to 12 months of DAPT, without significantly increasing the risk of stent thrombosis.4 Thus, in a low-risk population given available second-generation DES technology, DAPT duration of 1 year used in the interruption group of the ARCTIC-Interruption trial1 compared with shorter DAPT duration might not be beneficial in terms of the incidence of ischaemic events, but might be associated with an increased rate of bleedings. Thus, as suggested by present guidelines,5 DAPT duration of 1 year can no longer be recommended in low-risk patients.
David Parker/Science Photo Library
Effects of long-term use of cardiovascular drugs
We declare no competing interests.
*Johann Auer, Robert Berent [email protected] General Hospital Braunau, Cardiology and Intensive Care, Braunau A-5280, Austria
Dual antiplatelet treatment after stenting
1
With great interest, we read the study by Jean-Philippe Collet and colleagues (Nov 1, p 1577) 1 who found no ischaemic benefit for extension of dual antiplatelet treatment (DAPT) beyond 1 year after stenting with drug-eluting stent (DES) when no event has occurred within the first year after
2
3
Collet J-P, Silvain J, Barthélémy O, et al. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014; 384: 1577–85. Cassese S, Byrne RA, Tada T, King LA, Kastrati A. Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials. Eur Heart J 2012; 33: 3078–87. Colombo A, Chieffo A, Frasheri A, et al. Second generation drug-eluting stents implantation followed by six- versus twelve-month dual antiplatelet therapy: the SECURITY randomised clinical trial. J Am Coll Cardiol 2014; 64: 2086–97.
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
325
Millions of people are prescribed drugs to prevent and treat cardiovascular disease for decades, even though the long-term safety and efficacy of these drugs are unknown. Introduction of the polypill (typically containing aspirin, statin, beta-blocker, and angiotensin-converting-enzyme inhibitor) without evidence of its long-term effects provides an additional challenge. This concern is particularly relevant to beta-blockers. DGJ experienced two potentially fatal events almost certainly due to the drug. After the first event, he was identified to have hypotension on exercise; after the second, he was diagnosed with extreme bradycardia due to sinoatrial block. Both abnormalities ceased when beta-blockers were stopped. If he had died, his death would not have been attributed to the drug. Should beta-blockers be prescribed in the long term in the absence of angina symptoms or heart failure? Some publications have questioned the effectiveness of beta-blockers in preventing death and recurrent infarction.1,2 Meta-analyses suggest no beneficial effect of beta-blockers on mortality in chronic stable angina, 3,4 and a review 2 into their use after myocardial infarction questioned their value after the first year or so, at least in those with preserved ventricular function. The effectiveness and safety of drugs might change with age of the individual. There might be other drugs, besides beta-blockers, which although beneficial in the short term, might have harmful effects in the long term. For instance, the long-term use of high-dose statins over decades might not be warranted. The potential harm caused by long-term use of treatments in elderly people should be a priority for organisations responsible for drug safety—eg, regulatory agencies www.thelancet.com Vol 385 January 24, 2015
such as the US Food and Drug Administration and the European Medicines Agency—but does not seem to be one. Post-approval long-term studies should be done. Randomised trials of withdrawal versus continuation of drugs (eg, beta-blockers) are also needed.5 We need reliable evidence to establish when to stop long-term use of cardiovascular drugs that are effective and safe in the short term. Improved data for whether elderly patients might be harmed by continuance of drug treatments prescribed many years earlier is needed.6 We declare no competing interests.
Desmond G Julian, *Stuart J Pocock [email protected] Netherhall Gardens, London NW3 5RN, UK (DGJ); and London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK (SJP) 1
2
3
4
5
6
Bangalore S, Steg PG, Deedwania P, et al. Beta-blocker use and clinical outcomes in stable outpatients with and without coronary artery disease. JAMA 2012; 308: 1340–49. Kezerashvile A, Marzo K, De Leon J. Beta-blocker use after acute myocardial infarction in the patient with normal systolic function: when is it “ok” to discontinue? Curr Cardiol Rev 2012; 8: 77–84. Huang HL, Fox KA. The impact of beta-blockers on mortality in stable angina: a meta-analysis. Scott Med J 2012; 57: 69–75. Shu de F, Dong BR, Lin XF, Wu TX, Liu GJ. Long-term beta blockers for stable anginas: systematic review and meta-analysis. Eur J Prev Cardiol 2012; 19: 330–41. Pocock SJ, Gersh BJ. Do current clinical trials meet society’s needs? A critical review of recent evidence. JACC 2014; 64: 1615–28. Gnjidic D, Le Couteur DG, Hilmer SN. Discontinuing drug treatments: we need better evidence to guide deprescribing. BMJ 2014; 349: g7013.
stenting. By contrast, a strategy of prolongation of DAPT for up to 2 years might be harmful because of increased major or minor bleedings in the continuation group.2 However, previous data could show that in a low-risk population, like the one included in this study, DAPT duration of only 6 months after second-generation DES implantation is not inferior compared with 12 months of DAPT in terms of the incidence of cardiac death, myocardial infarction, stroke, definite or probable stent thrombosis, and major bleedings at 12 months.3 Even a shorter duration of DAPT (3 months) in patients with stable coronary artery disease or low-risk acute coronary syndrome given second-generation DES was not inferior to 12 months of DAPT, without significantly increasing the risk of stent thrombosis.4 Thus, in a low-risk population given available second-generation DES technology, DAPT duration of 1 year used in the interruption group of the ARCTIC-Interruption trial1 compared with shorter DAPT duration might not be beneficial in terms of the incidence of ischaemic events, but might be associated with an increased rate of bleedings. Thus, as suggested by present guidelines,5 DAPT duration of 1 year can no longer be recommended in low-risk patients.
David Parker/Science Photo Library
Effects of long-term use of cardiovascular drugs
We declare no competing interests.
*Johann Auer, Robert Berent [email protected] General Hospital Braunau, Cardiology and Intensive Care, Braunau A-5280, Austria
Dual antiplatelet treatment after stenting
1
With great interest, we read the study by Jean-Philippe Collet and colleagues (Nov 1, p 1577) 1 who found no ischaemic benefit for extension of dual antiplatelet treatment (DAPT) beyond 1 year after stenting with drug-eluting stent (DES) when no event has occurred within the first year after
2
3
Collet J-P, Silvain J, Barthélémy O, et al. Dual-antiplatelet treatment beyond 1 year after drug-eluting stent implantation (ARCTIC-Interruption): a randomised trial. Lancet 2014; 384: 1577–85. Cassese S, Byrne RA, Tada T, King LA, Kastrati A. Clinical impact of extended dual antiplatelet therapy after percutaneous coronary interventions in the drug-eluting stent era: a meta-analysis of randomized trials. Eur Heart J 2012; 33: 3078–87. Colombo A, Chieffo A, Frasheri A, et al. Second generation drug-eluting stents implantation followed by six- versus twelve-month dual antiplatelet therapy: the SECURITY randomised clinical trial. J Am Coll Cardiol 2014; 64: 2086–97.
Submissions should be made via our electronic submission system at http://ees.elsevier.com/ thelancet/
325