- Email: [email protected]
Q waves to guide treatment of myocardial infarction
Comment
Q waves to guide treatment of myocardial infarction Despite tremendous advances in the primary and secondary prevention of coronary artery disease, ST-segment-elevation myocardial infarction (STEMI) still occurs in vast numbers. Mortality in the shortterm in patients with STEMI remains remarkably high: 8% 1-month mortality in the recent European Heart Survey1 and 12% inhospital mortality in the US National Registry of Myocardial Infarction 3 and 4.2,3 The key to reducing mortality in STEMI is rapid and sustained recanalisation of the infarct-related artery to reperfuse the myocardium it supplies. Large-scale randomised trials have shown the efficacy of two different approaches to reperfusion therapy: intravenous fibrinolytic therapy4 and primary percutaneous coronary intervention (PCI).5 Recent head-to-head trials with these strategies revealed the superiority of primary PCI in reducing stroke, non-fatal reinfarction, and death, even in patients requiring transfer for PCI.5,6 Despite these findings, however, fibrinolytic therapy remains the dominant strategy for reperfusion throughout the world because of low cost, ease of use, and widespread availability. Therefore, if primary PCI is not available to all patients with STEMI, we need to identify those who are likely to benefit from this form of therapy. Current guidelines confront this issue by addressing four factors: contraindications to fibrinolysis, presence or absence of shock or severe congestive heart failure, time from presentation to treatment, and time from onset of symptoms to presentation.7,8 The first two factors are “no-brainers”. Because of the non-trivial baseline risk of catastrophic haemorrhage associated with all fibrinolytics, a patient with a substantially increased risk of bleeding should undergo primary PCI even if transfer to another centre is required. Similarly, patients with cardiorespiratory decompensation derive a much larger benefit from primary PCI and therefore should also be selected for this treatment.9,10 Time from presentation to treatment is unarguably the most relevant factor, because extended delay in the ability to start primary PCI favours the use of fibrinolysis (the less effective but more available therapy). The fourth factor, time from onset of symptoms to presentation, is the most problematic. In today’s Lancet, Cheuk-Kit Wong and www.thelancet.com Vol 367 June 24, 2006
colleagues, on behalf of the HERO-2 investigators, report findings that shift the emphasis away from time to presentation to ECG at presentation.11 In this latest HERO-2 (Hirulog Early Reperfusion Occlusion) study, patients with STEMI presenting within 6 h of symptom onset were treated with fibrinolytic therapy (aspirin and streptokinase) and randomised to either the direct-thrombin inhibitor bivalirudin or unfractionated heparin.12 Baseline ECG traces for over 15 000 patients with normal intraventricular conduction were analysed and divided into those with or without pathological Q waves at presentation. Somewhat surprisingly, by strict criteria, more than two-thirds of patients had Q waves in the infarct territory at the time of presentation. Patients with initial Q waves had an absolute 30-day mortality just over 3% higher than patients without initial Q waves (10% vs 7%). Even in patients randomised very early after symptom onset (0–2 h), mortality in patients with initial Q waves was high (8%). Remarkably, 30-day mortality was similarly high in patients with initial Q waves randomised in 2 h or less and patients without Q waves randomised 4 h or more after symptom onset. In separate multivariate analyses, both initial Q waves and time to randomisation were independently predictive of mortality. However, when both factors were included, the presence of initial Q waves remained predictive of a 44% increase in the odds of death, whereas time to randomisation was no longer predictive of mortality. Why should the presence of Q waves outperform time to presentation as a predictor of outcome? Perhaps most important is the subjective nature of a patient’s recollection of the onset of symptoms: in the throes of a heart attack, who looks at their watch? Many patients have symptoms that wax and wane—when did sustained occlusion of the infarct artery actually occur? And how do we classify the large group of patients who present with atypical chest pain or no chest pain at all? Furthermore, the pace of myocardial necrosis depends on factors other than the duration of occlusion of the infarct artery, such as ischaemic preconditioning, collateral flow, and the level of oxygen demand.13 Although these facts have been known for years, the HERO-2 study provides solid
See Articles page 2061
2035
Comment
Panel: Factors favouring primary percutaneous coronary intervention over fibrinolysis for treatment of ST-elevation myocardial infarction ●
● ● ● ● ●
●
Ability to implement primary percutaneous coronary intervention within 120 min from presentation irrespective of all other factors Q waves on initial ECG Time-to-presentation >3 h Cardiogenic shock Severe heart failure and/or pulmonary oedema Contraindication to fibrinolysis - History of intracranial haemorrhage - Substantial risk of intracranial haemorrhage (based on age, sex, weight) - Known structural cerebral vascular disease or malignant intracranial neoplasm - Ischaemic stroke within 3 months - Active bleeding or bleeding diathesis - Significant closed head or facial trauma within 3 months - History of chronic, severe, poorly controlled hypertension - Uncontrolled hypertension on presentation (irrespective of response to therapy) - Major surgery within 3 weeks - Recent internal bleeding - Previous exposure or allergy (for streptokinase) - Non-compressible vascular puncture - Pregnancy - Active peptic ulcer - Current use of anticoagulants Diagnosis of ST-segment elevation myocardial infarction is in doubt
2 h of symptom onset and had no initial Q waves. Therefore, if we add the presence of initial Q waves to established criteria favouring primary PCI (panel),7,8 we find that primary PCI is favoured in virtually all patients with STEMI. With the huge public-health implications of STEMI treatment, this conclusion mandates the rapid development and implementation of protocols to allow universal access to timely and skilled performance of this life-saving procedure. At least in the USA, a report suggests that such protocols are feasible with the current access of most of the population to PCI-capable facilities.14 Once such systems are universally in place, the use of fibrinolysis will be reserved for those few patients with definite early presentation, no Q waves on the initial ECG, haemodynamic stability, low risk of haemorrhage, and insurmountable logistical considerations precluding timely access to skilled primary PCI. *Howard Cooper, Julio A Panza Coronary Care Unit, Washington Hospital Center, Washington DC 20010, USA [email protected] We declare that we have no conflict of interest. 1
2
3
objective evidence of the need to combine time to presentation with ECG findings to determine the best treatment strategy in STEMI. How then should we incorporate these data into clinical practice? The HERO-2 investigators suggest that, in patients who present within 2–3 h or less and have no Q waves on the initial ECG, fibrinolysis seems to afford the greatest survival benefit and therefore might be preferred. In all other patients with STEMI, the authors contend, primary PCI would be preferred. Although this conclusion requires a large extrapolation from a study in which neither the benefits of fibrinolysis nor its relative merits compared with primary PCI were assessed, it does fit within the broader context of data strongly favouring primary PCI for patients at the highest level of risk. Of note, in the HERO-2 trial, only 8% of patients presented within 2036
4
5
6
7
8
9
Hasdai D, Behar S, Wallentin L, et al. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J 2002; 23: 1190–201. Rogers WJ, Bowlby LJ, Chandra NC, et al. Treatment of myocardial infarction in the United States (1990 to 1993). Observations from the National Registry of Myocardial Infarction. Circulation 1994; 90: 2103–14. Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol 2000; 36: 2056–63. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311–22. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13–20. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation 2003; 108: 1809–14. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004; 44: E1–211. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003; 24: 28–66. Hochman JS, Sleeper LA, Webb JG, for the SHOCK Investigators. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999; 341: 625–34.
www.thelancet.com Vol 367 June 24, 2006
Comment
10
11
12
Wu AH, Parsons L, Every NR, Bates ER. Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol 2002; 40: 1389–94. Wong C-K, Gao W, Raffel OC, for the HERO-2 Investigators. Initial Q waves accompanying ST-segment elevation at presentation of acute myocardial infarction and 30-day mortality in patients given streptokinase therapy: an analysis from HERO-2. Lancet 2006; 367: 2061–67. White H, Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Thrombin-specific anticoagulation with bivalirudin versus
13
14
heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001; 358: 1855–63. Reimer KA, Jennings RB, Cobb FR, et al. Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models. Circ Res 1985; 56: 651–65. Nallamothu BK, Bates ER, Wang Y, Bradley EH, Krumholz HM. Driving times and distances to hospitals with percutaneous coronary intervention in the United States: implications for prehospital triage of patients with ST-elevation myocardial infarction. Circulation 2006; 113: 1189–95.
Artemisinin combination therapies
www.thelancet.com Vol 367 June 24, 2006
only coformulated ACT. Coformulation prevents inappropriate drug use that can occur when different pills are administered together. Furthermore, South Africa rapidly contained a deadly malaria epidemic in KwaZulu-Natal by using artemether-lumefantrine with other antimalarial measures in 2000–01.2 However, the promise of artemether-lumefantrine remains unfulfilled. There has not been enough drug to meet surging demand, and because of cost ACTs remain first-line therapy as policy but not as practice in many countries. Furthermore, reports of treatment failure emerged soon after artemether-lumefantrine was introduced in Zanzibar, with genetic evidence for selection of lumefantrine-resistant parasites.3,4
See Articles page 2075
We do not have the rights to reproduce this image on the web.
Science Photo Library
Global mortality from Plasmodium falciparum malaria has always been enormous, and has increased in recent decades as chloroquine-resistant parasites spread worldwide. Alarms were raised further when parasites developed resistance to sulfadoxine-pyrimethamine soon after it was introduced to replace chloroquine in many areas. To protect the few remaining drugs in the malaria armamentarium, combination therapy is now touted, particularly combinations that include artemisinin derivatives, widely known as artemisinin combination therapies (ACTs). Artemisinins are appealing. They work quickly, appear safe and well-tolerated, and might decrease malaria transmission by inactivating or killing gametocytes (the parasite form that transmits to mosquitoes). Several ACTs exist that differ either in the artemisinin derivative or its partner drug. Choosing the right ACT is very important for Ministries of Health. However, little is known about the comparative efficacy or sustainability of the different ACTs. In today’s Lancet, Frank Smithuis and colleagues compare two ACTs, dihydroartemisinin-piperaquine and artesunate-mefloquine, for treating falciparum malaria.1 They found that both combinations were highly efficacious and effective in Burma. Artesunate-mefloquine was recently introduced as first-line treatment in Burma, but the ineffective drug chloroquine is still widely used because of the high cost of artesunate-mefloquine. The researchers note that dihydroartemisinin-piperaquine (about US$1·50 per adult treatment) is much cheaper than artesunate-mefloquine (about $3). Should everyone be switching to dihydroartemisinin-piperaquine? Most countries in Africa, where antimalarial resistance has been an unmitigated disaster, are switching to artemether-lumefantrine. Until recently, this was the
Scanning electron micrograph of red blood cells and Plasmodium falciparum
2037
Q waves to guide treatment of myocardial infarction Despite tremendous advances in the primary and secondary prevention of coronary artery disease, ST-segment-elevation myocardial infarction (STEMI) still occurs in vast numbers. Mortality in the shortterm in patients with STEMI remains remarkably high: 8% 1-month mortality in the recent European Heart Survey1 and 12% inhospital mortality in the US National Registry of Myocardial Infarction 3 and 4.2,3 The key to reducing mortality in STEMI is rapid and sustained recanalisation of the infarct-related artery to reperfuse the myocardium it supplies. Large-scale randomised trials have shown the efficacy of two different approaches to reperfusion therapy: intravenous fibrinolytic therapy4 and primary percutaneous coronary intervention (PCI).5 Recent head-to-head trials with these strategies revealed the superiority of primary PCI in reducing stroke, non-fatal reinfarction, and death, even in patients requiring transfer for PCI.5,6 Despite these findings, however, fibrinolytic therapy remains the dominant strategy for reperfusion throughout the world because of low cost, ease of use, and widespread availability. Therefore, if primary PCI is not available to all patients with STEMI, we need to identify those who are likely to benefit from this form of therapy. Current guidelines confront this issue by addressing four factors: contraindications to fibrinolysis, presence or absence of shock or severe congestive heart failure, time from presentation to treatment, and time from onset of symptoms to presentation.7,8 The first two factors are “no-brainers”. Because of the non-trivial baseline risk of catastrophic haemorrhage associated with all fibrinolytics, a patient with a substantially increased risk of bleeding should undergo primary PCI even if transfer to another centre is required. Similarly, patients with cardiorespiratory decompensation derive a much larger benefit from primary PCI and therefore should also be selected for this treatment.9,10 Time from presentation to treatment is unarguably the most relevant factor, because extended delay in the ability to start primary PCI favours the use of fibrinolysis (the less effective but more available therapy). The fourth factor, time from onset of symptoms to presentation, is the most problematic. In today’s Lancet, Cheuk-Kit Wong and www.thelancet.com Vol 367 June 24, 2006
colleagues, on behalf of the HERO-2 investigators, report findings that shift the emphasis away from time to presentation to ECG at presentation.11 In this latest HERO-2 (Hirulog Early Reperfusion Occlusion) study, patients with STEMI presenting within 6 h of symptom onset were treated with fibrinolytic therapy (aspirin and streptokinase) and randomised to either the direct-thrombin inhibitor bivalirudin or unfractionated heparin.12 Baseline ECG traces for over 15 000 patients with normal intraventricular conduction were analysed and divided into those with or without pathological Q waves at presentation. Somewhat surprisingly, by strict criteria, more than two-thirds of patients had Q waves in the infarct territory at the time of presentation. Patients with initial Q waves had an absolute 30-day mortality just over 3% higher than patients without initial Q waves (10% vs 7%). Even in patients randomised very early after symptom onset (0–2 h), mortality in patients with initial Q waves was high (8%). Remarkably, 30-day mortality was similarly high in patients with initial Q waves randomised in 2 h or less and patients without Q waves randomised 4 h or more after symptom onset. In separate multivariate analyses, both initial Q waves and time to randomisation were independently predictive of mortality. However, when both factors were included, the presence of initial Q waves remained predictive of a 44% increase in the odds of death, whereas time to randomisation was no longer predictive of mortality. Why should the presence of Q waves outperform time to presentation as a predictor of outcome? Perhaps most important is the subjective nature of a patient’s recollection of the onset of symptoms: in the throes of a heart attack, who looks at their watch? Many patients have symptoms that wax and wane—when did sustained occlusion of the infarct artery actually occur? And how do we classify the large group of patients who present with atypical chest pain or no chest pain at all? Furthermore, the pace of myocardial necrosis depends on factors other than the duration of occlusion of the infarct artery, such as ischaemic preconditioning, collateral flow, and the level of oxygen demand.13 Although these facts have been known for years, the HERO-2 study provides solid
See Articles page 2061
2035
Comment
Panel: Factors favouring primary percutaneous coronary intervention over fibrinolysis for treatment of ST-elevation myocardial infarction ●
● ● ● ● ●
●
Ability to implement primary percutaneous coronary intervention within 120 min from presentation irrespective of all other factors Q waves on initial ECG Time-to-presentation >3 h Cardiogenic shock Severe heart failure and/or pulmonary oedema Contraindication to fibrinolysis - History of intracranial haemorrhage - Substantial risk of intracranial haemorrhage (based on age, sex, weight) - Known structural cerebral vascular disease or malignant intracranial neoplasm - Ischaemic stroke within 3 months - Active bleeding or bleeding diathesis - Significant closed head or facial trauma within 3 months - History of chronic, severe, poorly controlled hypertension - Uncontrolled hypertension on presentation (irrespective of response to therapy) - Major surgery within 3 weeks - Recent internal bleeding - Previous exposure or allergy (for streptokinase) - Non-compressible vascular puncture - Pregnancy - Active peptic ulcer - Current use of anticoagulants Diagnosis of ST-segment elevation myocardial infarction is in doubt
2 h of symptom onset and had no initial Q waves. Therefore, if we add the presence of initial Q waves to established criteria favouring primary PCI (panel),7,8 we find that primary PCI is favoured in virtually all patients with STEMI. With the huge public-health implications of STEMI treatment, this conclusion mandates the rapid development and implementation of protocols to allow universal access to timely and skilled performance of this life-saving procedure. At least in the USA, a report suggests that such protocols are feasible with the current access of most of the population to PCI-capable facilities.14 Once such systems are universally in place, the use of fibrinolysis will be reserved for those few patients with definite early presentation, no Q waves on the initial ECG, haemodynamic stability, low risk of haemorrhage, and insurmountable logistical considerations precluding timely access to skilled primary PCI. *Howard Cooper, Julio A Panza Coronary Care Unit, Washington Hospital Center, Washington DC 20010, USA [email protected] We declare that we have no conflict of interest. 1
2
3
objective evidence of the need to combine time to presentation with ECG findings to determine the best treatment strategy in STEMI. How then should we incorporate these data into clinical practice? The HERO-2 investigators suggest that, in patients who present within 2–3 h or less and have no Q waves on the initial ECG, fibrinolysis seems to afford the greatest survival benefit and therefore might be preferred. In all other patients with STEMI, the authors contend, primary PCI would be preferred. Although this conclusion requires a large extrapolation from a study in which neither the benefits of fibrinolysis nor its relative merits compared with primary PCI were assessed, it does fit within the broader context of data strongly favouring primary PCI for patients at the highest level of risk. Of note, in the HERO-2 trial, only 8% of patients presented within 2036
4
5
6
7
8
9
Hasdai D, Behar S, Wallentin L, et al. A prospective survey of the characteristics, treatments and outcomes of patients with acute coronary syndromes in Europe and the Mediterranean basin; the Euro Heart Survey of Acute Coronary Syndromes (Euro Heart Survey ACS). Eur Heart J 2002; 23: 1190–201. Rogers WJ, Bowlby LJ, Chandra NC, et al. Treatment of myocardial infarction in the United States (1990 to 1993). Observations from the National Registry of Myocardial Infarction. Circulation 1994; 90: 2103–14. Rogers WJ, Canto JG, Lambrew CT, et al. Temporal trends in the treatment of over 1.5 million patients with myocardial infarction in the US from 1990 through 1999: the National Registry of Myocardial Infarction 1, 2 and 3. J Am Coll Cardiol 2000; 36: 2056–63. Fibrinolytic Therapy Trialists’ (FTT) Collaborative Group. Indications for fibrinolytic therapy in suspected acute myocardial infarction: collaborative overview of early mortality and major morbidity results from all randomised trials of more than 1000 patients. Lancet 1994; 343: 311–22. Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet 2003; 361: 13–20. Dalby M, Bouzamondo A, Lechat P, Montalescot G. Transfer for primary angioplasty versus immediate thrombolysis in acute myocardial infarction: a meta-analysis. Circulation 2003; 108: 1809–14. Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1999 Guidelines for the Management of patients with acute myocardial infarction). J Am Coll Cardiol 2004; 44: E1–211. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology. Management of acute myocardial infarction in patients presenting with ST-segment elevation. Eur Heart J 2003; 24: 28–66. Hochman JS, Sleeper LA, Webb JG, for the SHOCK Investigators. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. N Engl J Med 1999; 341: 625–34.
www.thelancet.com Vol 367 June 24, 2006
Comment
10
11
12
Wu AH, Parsons L, Every NR, Bates ER. Hospital outcomes in patients presenting with congestive heart failure complicating acute myocardial infarction: a report from the Second National Registry of Myocardial Infarction (NRMI-2). J Am Coll Cardiol 2002; 40: 1389–94. Wong C-K, Gao W, Raffel OC, for the HERO-2 Investigators. Initial Q waves accompanying ST-segment elevation at presentation of acute myocardial infarction and 30-day mortality in patients given streptokinase therapy: an analysis from HERO-2. Lancet 2006; 367: 2061–67. White H, Hirulog and Early Reperfusion or Occlusion (HERO)-2 Trial Investigators. Thrombin-specific anticoagulation with bivalirudin versus
13
14
heparin in patients receiving fibrinolytic therapy for acute myocardial infarction: the HERO-2 randomised trial. Lancet 2001; 358: 1855–63. Reimer KA, Jennings RB, Cobb FR, et al. Animal models for protecting ischemic myocardium: results of the NHLBI Cooperative Study. Comparison of unconscious and conscious dog models. Circ Res 1985; 56: 651–65. Nallamothu BK, Bates ER, Wang Y, Bradley EH, Krumholz HM. Driving times and distances to hospitals with percutaneous coronary intervention in the United States: implications for prehospital triage of patients with ST-elevation myocardial infarction. Circulation 2006; 113: 1189–95.
Artemisinin combination therapies
www.thelancet.com Vol 367 June 24, 2006
only coformulated ACT. Coformulation prevents inappropriate drug use that can occur when different pills are administered together. Furthermore, South Africa rapidly contained a deadly malaria epidemic in KwaZulu-Natal by using artemether-lumefantrine with other antimalarial measures in 2000–01.2 However, the promise of artemether-lumefantrine remains unfulfilled. There has not been enough drug to meet surging demand, and because of cost ACTs remain first-line therapy as policy but not as practice in many countries. Furthermore, reports of treatment failure emerged soon after artemether-lumefantrine was introduced in Zanzibar, with genetic evidence for selection of lumefantrine-resistant parasites.3,4
See Articles page 2075
We do not have the rights to reproduce this image on the web.
Science Photo Library
Global mortality from Plasmodium falciparum malaria has always been enormous, and has increased in recent decades as chloroquine-resistant parasites spread worldwide. Alarms were raised further when parasites developed resistance to sulfadoxine-pyrimethamine soon after it was introduced to replace chloroquine in many areas. To protect the few remaining drugs in the malaria armamentarium, combination therapy is now touted, particularly combinations that include artemisinin derivatives, widely known as artemisinin combination therapies (ACTs). Artemisinins are appealing. They work quickly, appear safe and well-tolerated, and might decrease malaria transmission by inactivating or killing gametocytes (the parasite form that transmits to mosquitoes). Several ACTs exist that differ either in the artemisinin derivative or its partner drug. Choosing the right ACT is very important for Ministries of Health. However, little is known about the comparative efficacy or sustainability of the different ACTs. In today’s Lancet, Frank Smithuis and colleagues compare two ACTs, dihydroartemisinin-piperaquine and artesunate-mefloquine, for treating falciparum malaria.1 They found that both combinations were highly efficacious and effective in Burma. Artesunate-mefloquine was recently introduced as first-line treatment in Burma, but the ineffective drug chloroquine is still widely used because of the high cost of artesunate-mefloquine. The researchers note that dihydroartemisinin-piperaquine (about US$1·50 per adult treatment) is much cheaper than artesunate-mefloquine (about $3). Should everyone be switching to dihydroartemisinin-piperaquine? Most countries in Africa, where antimalarial resistance has been an unmitigated disaster, are switching to artemether-lumefantrine. Until recently, this was the
Scanning electron micrograph of red blood cells and Plasmodium falciparum
2037