In-Hospital Initiation of Cardiovascular Protective Medications for Patients Undergoing Percutaneous Coronary Intervention: Taki

Percutaneous coronary interventional (PCI) procedures have changed the face of cardiovascular care, providing significant improvements in quality of life and survival for patients with debilitating cardiac disease. In 2000, there were over 500,000 patients who underwent PCI procedures in the United States.1 Although these coronary procedures have become routine, they do not modify the underlying disease process of atherosclerosis; they only reduce ischemia by mechanically increasing blood flow. Even when completely revascularized and in the absence of stress-induced ischemia, cardiovascular disease patients remain at increased risk for cardiovascular events, repeat hospitalizations and mortality.2 Cardiovascular protective medical therapy is the only treatment that changes the underlying atherosclerotic disease process. There is compelling clinical trial evidence that antiplatelet, beta-blocker, angiotensin-converting enzyme (ACE) inhibitor, and lipid-lowering therapy reduces the risk of cardiovascular events and hospitalizations as well as substantially improves survival in patients after percutaneous coronary intervention (PCI).2–6 Despite this evidence, as well as national and international clinical guidelines recommending these cardiovascular protective treatments in patients with coronary heart disease (CHD) including patients after PCI, a number of studies have documented low treatment rates in this patient population.7–12 The conventional approach to the initiation of lipid-lowering therapy was to delay therapy while in-hospital; instead, the national guidelines recommended waiting a period of time until patients were metabolically stable as an outpatient.13 Unfortunately, in the majority of PCI patients and other CHD patients, lipid-lowering therapy does not get initiated during outpatient follow-up. Based on the scientific evidence demonstrating that in-hospital initiation of lipid-lowering and other cardiovascular protective medications resulted in a marked increase in treatment rates, improved long-term patient compliance and improved clinical outcomes, this approach has been integrated into the National Cholesterol Education Program Adult Treatment Panel III, American Heart Association (AHA)/American College of Cardiology (ACC) Secondary Prevention Guidelines, and ACC/AHA Acute Coronary Syndromes Guidelines and is now considered the standard of care.2–4 The under-use of cardiovascular protective therapies in patients after PCI represents a major clinical practice and public health issue.1,14 This article will review the rationale for in-hospital initiation of cardiovascular protective therapies in PCI patients, successful hospital-based programs that have been demonstrated to improve treatment rates, and present the evidence supporting in-hospital initiation of cardiovascular protective medications as the standard of care in patients hospitalized for PCI. Cardiovascular risk after PCI. This year, over 550,000 individuals in the United States will have a cardiac revascularization procedure.1 The majority of cardiovascular events result from atherosclerotic plaques that were previously non-obstructive; as such, the cardiovascular risk after PCI remains substantial. Within 4 years of PCI, thirty percent of patients will have a major cardiovascular event. Patients with a prior history of PCI are 5–7 times more likely to sustain a cardiovascular event compared to individuals without clinically evident atherosclerotic vascular disease.1 These post-PCI patients remain at risk for recurrent events even if they are entirely asymptomatic, even if they have no demonstrated ischemia on stress testing, and even if they have undergone complete revascularization. Patients after PCI thus constitute a high-risk group for cardiovascular events, recurrent hospitalizations and cardiovascular mortality. Benefits of cardiovascular protective medications. There is compelling evidence that antiplatelet therapy, beta-blockers, ACE inhibitors and lipid-lowering therapy each reduce the risk of cardiovascular events, recurrent hospitalizations and mortality in patients after PCI.2–5 Each of these therapies individually have been demonstrated to have early as well as long-term benefits in patients with coronary artery disease, patients with acute coronary syndromes and patients after PCI. Meta-analyses of randomized placebo-controlled clinical trials in patients with CHD have shown a 20–25% relative risk reduction with antiplatelet therapy, a 20–30% relative risk reduction with beta-blockers and a 20–25% risk reduction with ACE inhibitors.2,5,6,15 Lipid-lowering therapy with HMG CoA reductase inhibitors (statins) has been associated with a 22–42% reduction in cardiovascular risk in CHD patients.2,15–18 The benefits of these cardiovascular protective medications have been shown to directly apply to patients after PCI. The Lescol Intervention Prevention Study (LIPS) randomized patients on an average of 2 days after successful PCI to fluvastatin 40 mg twice per day or placebo.18 Statin therapy reduced long-term clinical events by 22% (Figure 1). This trial established the safety and long-term benefit of the use of statins initiated shortly after PCI. The safety of in-hospital initiation of statin therapy after an acute coronary syndrome (ACS), whether managed invasively or conservatively, has also been demonstrated in other prospective randomized clinical trials, including the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial and the Pravastatin Acute Coronary Treatment (PACT) trial.19,20 Together, these trials have included 8,171 patients with no significant adverse effects to in-hospital initiated statin therapy overall or in the subgroup of patients with low levels of total cholesterol at initiation. There is compelling evidence that post-PCI patients benefit from statin therapy irrespective of baseline low-density lipoprotein (LDL) cholesterol. The Heart Protection Study (HPS) randomized atherosclerotic or diabetic patients to simvastatin 40 mg per day versus placebo, including 3,421 patients with baseline LDL below 100 mg/dl.17 Not only did these patients derive major clinical benefits, the relative risk reduction with simvastatin was similar to those patients with much higher baseline LDL. In LIPS, the benefit from fluvastatin was seen whether the baseline LDL was above or below the mean of 132 mg/dl.17 On the basis of these trails, statin therapy can be recommended for all post-coronary event and post-PCI patients irrespective of the level of total or LDL cholesterol, in the absence of contraindications. Patients undergoing successful PCI have been shown to have a marked long-term survival benefit from beta-blocker therapy. In a prospective analysis of 4,553 PCI patients comparing the 2,056 (45%) that were treated with beta-blockers at the time of the procedure to those that were not, beta-blocker therapy was associated with a mortality reduction from 6.0% to 3.9% at 1 year (p = 0.0014).21 Beta-blocker therapy is also the most effective class of medication against sudden cardiac death. The Heart Outcomes Prevention Evaluation (HOPE) study demonstrated the significant benefits of ACE inhibition in patients with documented coronary, cerebral, peripheral vascular disease or diabetes.22 This study assessed the effects of treatment with the ACE inhibitor ramipril versus placebo in 9,297 patients who had evidence of vascular disease or diabetes plus 1 additional cardiovascular risk factor and who did not have left ventricular dysfunction or heart failure. Treatment with ramipril resulted in reduced rates of death from cardiovascular causes or any cause, myocardial infarction, stroke, revascularization procedures, cardiac arrest and heart failure. Substantial benefits with ACE inhibitors were seen in patients after PCI and after coronary artery bypass grafting surgery.22 The benefits of long-term antiplatelet therapy with aspirin are well documented in post-PCI patients.2,3 More recently, the benefits of 12 months of combination antiplatelet therapy with aspirin and clopidogrel after PCI have been demonstrated in the CREDO trial.23 Review of recent clinical trials has failed to identify significant subgroups of post-PCI patients that failed to benefit from each of the proven cardiovascular protective therapies.2,18,22,23 Thus, the vast majority of PCI patients would be expected to be appropriate candidates and to benefit from the use of the combination of these cardiovascular protective medications. The benefits of the cardiovascular protective medications have been shown to be additive. Patients derived substantial risk reductions even when receiving each of the other 3 classes of medications with the addition of the fourth medication. In the HOPE trial, the addition of the ACE inhibitor ramipril was additive to aspirin, beta-blocker and lipid lowering therapy.22 In HPS, simvastatin provided additive cardiovascular risk reduction to aspirin, beta-blockers and ACE inhibitors.17 The cumulative benefit of using all 4 classes of medications in combination is estimated to be of the magnitude of a 70–75% reduction in relative risk for cardiovascular events or death (Table 1).15,24 The magnitude of benefit with antiplatelet, beta-blockers and ACE inhibitors, and lipid-lowering medications, matches or exceeds the benefits seen with revascularization.3,14 The gap in applying guideline-recommended therapy after PCI. Despite the wealth of scientific evidence and guideline recommendations regarding effective risk-reducing therapy after PCI, there has been an extensive body of evidence documenting that post-PCI patients have been receiving inadequate treatment to reduce their risk of cardiovascular events, and that guidelines have been failing to fulfill their purpose.7–12 Despite this compelling evidence and the recommendations of national guidelines, use of these drugs after PCI remains suboptimal. A variety of studies have reported substantial under-use of therapies such as aspirin, beta-blockers and ACE inhibitors in ideal post-PCI patients without documented contraindications or intolerance.8,9,12,21,25,26 A study of over 138,000 patients enrolled in the National Registry of Myocardial Infarction found that only 31.7% of patients hospitalized with an acute myocardial infarction (MI) received lipid-lowering therapy upon discharge.8 Under-use was seen in both men and women, across all age groups, and in the 34.8% of patients who had undergone PCI during the MI hospitalization. A number of other clinical, demographic, treatment and process of care factors that significantly influenced treatment utilization of lipid-lowering medications were also identified. Gaps in the use of aspirin, beta-blockers and ACE inhibitors in the absence of contraindications were also demonstrated in this patient population (Figure 2).11 Among the 20,809 patients hospitalized with an acute coronary syndrome and enrolled in the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) trial or Global Use of Streptokinase or t-PA for Occluded Coronary Arteries (GUSTO) IIb trial, only 3,653 patients (17.6%) were discharged on lipid-lowering therapy.25 In a study of 5,052 patients undergoing PCI at a major university teaching hospital, only 26.5% of patients were treated with lipid-lowering therapy, forty-four percent with beta-blockers, and 20% with ACE inhibitors.26 The treatment gap that begins in the hospital under conventional management continues on an outpatient basis. The Quality Assurance Project (QAP) analyzed treatment rates in 48,586 outpatients with documented CHD from 140 medical practices (80% cardiology) and found that only 39% of these patients were treated with lipid-lowering medications and only 11% were documented to have LDL cholesterol Barriers to implementing cardiovascular risk reduction. A number of barriers to implementing cardiovascular reducing therapy in patients with CHD were highlighted at the 27th American College of Cardiology Bethesda Conference.29 These included physicians being focused on acute problems, time constraints and lack of incentives, lack of training and poor communication between specialists and primary care physicians (Table 2). Provider awareness of the national guidelines has been shown to be insufficient to ensure effective implementation of cardiovascular protective therapies. In the L-TAP study, ninety-five percent of the surveyed physicians reported that they were knowledgeable on the NCEP guidelines and 65% reported they follow the guidelines on most patients, yet only 18% of outpatients with CHD undergoing treatment for hyperlipidemia by these physicians had an LDL cholesterol Does in-hospital initiation of cardiovascular protective therapy improve treatment use and clinical outcomes? Institution of cardiovascular protective therapy in the inpatient setting for patients undergoing PCI has a number of advantages.24 The structured setting within the hospital can facilitate the initiation of cardiovascular protective therapies though the use of physician prompts and reminders such as pre-printed order sets, discharge forms and involvement of other healthcare professionals.24 Hospital-based initiation of therapy may help to alleviate patient concerns regarding medication tolerability and side effects. Linking the initiation of secondary prevention measures to the patient’s cardiac hospitalization and PCI conveys the message that this therapy is essential for the prevention of cardiovascular events and is an essential part of the patient’s long-term treatment.24,31 Proof of the concept that in-hospital initiation of lipid-lowering and other cardiovascular protective medications improves treatment rates and long-term patient compliance was provided by the University of California, Los Angeles Cardiovascular Hospitalization Atherosclerosis Management Program (CHAMP).32 This program, initiated in a university hospital setting in 1994, focused on in-hospital initiation of aspirin, statin (irrespective of baseline LDL cholesterol, titrated to achieve LDL cholesterol In-hospital initiation of cardiovascular protective therapy as the standard of care. The NCEP-ATP III, AHA/ACC Secondary Prevention 2001, and ACC/AHA Acute Coronary Syndromes 2002 guidelines recommend in-hospital initiation of lipid-lowering medications and other cardiovascular protective therapies in appropriately selected patients hospitalized with cardiovascular disease or for a cardiovascular procedure.2–4 Thus, in-hospital initiation of lipid-lowering therapy along with other cardiovascular medical therapies is now recommended as the standard of care in patients with CHD, including patients after PCI. In-hospital initiation of therapy can also work in a complementary fashion with outpatient preventative cardiology and disease management programs.14 With the initiation of therapy beginning in the hospital, fewer titration steps are necessary to achieve target doses. While studies have demonstrated that patients managed in outpatient disease management programs have improved treatment rates with cardiovascular protective therapies, these systems are often applied to a selected patient population representing only a small proportion of the patients with AMI receiving care in the healthcare delivery system from which the patients were drawn.38 In-hospital initiation of therapy can help to ensure that each of the cardiovascular protective medications is started in patients who will not have access to specialized outpatient preventative cardiology and disease management programs. Outpatient systems to ensure appropriate monitoring of patients and up-titration of medical therapy to target doses remain essential for the patients who will not be followed in a specialized program; these patients would still be expected to be better off on doses started in the hospital than never having this therapy initiated.14 As reviewed in this article, it has been clearly documented that not enough has been done to ensure the use of cardiovascular protective therapies in patients after PCI. Projecting available data nationwide, in the year 2002, over half of the patients discharged after PCI were not treated with all 4 of the key evidence-based, guideline-recommended classes of medications, in the absence of contraindications or intolerance. Under conventional management, fewer than 20% of these patients discharged without 1 or more of the cardiovascular protective medications will be started on an outpatient basis.14,28 A review of the evidence from recent trials and clinical studies provides a compelling argument for implementing a combination of cardiovascular protective medications in-hospital as part of a systematic approach to address the underlying atherosclerotic vascular disease process. By initiating cardiovascular protective medical therapy during hospitalization as part of an effective management plan, interventional cardiologists, other inpatient physicians and nurses can take advantage of the teachable moment, make a vital contribution to the elimination of the treatment gap, and dramatically reduce the death and disability caused by atherosclerotic vascular disease. With optimal use of cardiovascular protective medications in patients after PCI, as many as 21,000 additional lives could be saved each year. Conclusion. Despite compelling scientific evidence of the benefits of antiplatelet, beta-blocker, ACE inhibitor and lipid-lowering therapy, a substantial proportion of patients after PCI are not on treatment with these evidence-based, guideline-recommended therapies. Applying hospital-based systems to ensure initiation of cardiovascular protective therapies has been demonstrated to improve treatment rates, long-term patient compliance and clinical outcomes in patients with CAD. Widespread application of hospital-based cardiovascular protective treatment initiation programs for PCI patients could dramatically increase rates with these proven, cost-effective therapies and thus substantially reduce the risk of cardiovascular events, recurrent hospitalizations and death.

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