(Statins) and Fixed-dose Combination Products Containing a Statin

More documents

Recommendations

Info

Final Report Update 5 Drug Effectiveness Review Project Table 11. Inpatient trials of acute myocardial infarction or unstable angina (statins compared with placebo or usual care) Trial (Quality) Population de Lemos 2004 A to Z Trial (Phase Z) 138 (Fair) Thompson et al 2004 PACT 140 (Fair-Poor) Arntz et al 2000 L-CAD 135 (Fair) Liem et al 2002 FLORIDA 136 (Fair) MIRACL 139 (Fair) Den Hartog (Pilot Study) 137 (Poor) Either non-STelevation acute coronary syndrome or ST elevation MI with a total cholesterol level of 250 mg or lower Within 24 hours of onset of acute MI or unstable angina Acute MI and/or underwent emergency PTCA due to severe or unstable angina pectoris MI and 1 of the following: new or markedly increased chest pain lasting longer than 30 minutes, or a new pathological Q-wave Unstable angina or non- Q-wave MI Acute MI or unstable angina, hospitalized for less than 48 hours Baseline LDL Median 112 mg/dL (25th- 75th percentiles 94-131 mg/dL) Not reported Mean total cholesterol 219 mg/dL Pravastatin vs. usual care 176 mg/dL (131-240) vs. 172 mg/dL (132- 239) 135 mg/dL vs. 139 mg/dL Study duration Median 721 days (range 6 months to 24 months) % LDL reduction Simvastatin first vs. placebo first 1 month: 39% vs. +10% (P
Final Report Update 5 Drug Effectiveness Review Project The L-CAD study established that patients with acute coronary syndrome benefit from statin treatment. 135 In L-CAD, 126 patients were randomized to pravastatin 20 or 40 mg or usual care an average of 6 days after an acute myocardial infarction or emergency percutaneous transluminal coronary angioplasty due to severe or unstable angina. After 2 years of follow-up, there were fewer major coronary events in the pravastatin group (22.9% compared with 52%; P=0.005). There was no difference in all-cause mortality, but each group had only 2 deaths. An earlier pilot study 137 of pravastatin 40 mg compared with placebo enrolled patients hospitalized for less than 48 hours with acute myocardial infarction or unstable angina. After 3 months, there was no significant difference on any clinical endpoint, although there was a 25% reduction in low-density lipoprotein cholesterol in the pravastatin group. PACT 140 assessed outcomes at 30 days in patients with acute myocardial infarction or unstable angina randomly assigned to receive pravastatin 20 to 40 mg or placebo within 24 hours of the onset of chest pain. This study was rated fair-to-poor quality because of some differences in groups at baseline (higher total cholesterol in placebo group, more placebo patients on hormone replacement therapy, and more pravastatin patients on anticoagulants) and no reporting of randomization and allocation concealment methods. The primary endpoint (composite of death, recurrence of myocardial infarction, or readmission to hospital for unstable angina) occurred in 12% of patients. There was no significant reduction in the primary endpoint (relative risk reduction, 6.4%; 95% CI, –1.4 to +3.0), or on any individual component of the primary endpoint. In MIRACL, 139 a short-term (16 weeks) placebo-controlled trial of atorvastatin 80 mg in patients with unstable angina or non-Q-wave myocardial infarction, there was a significant reduction in major coronary events (death, nonfatal acute myocardial infarction, cardiac arrest with resuscitation, or recurrent symptomatic myocardial infarction requiring emergency rehospitalization) in the atorvastatin group (17.4% compared with 14.8%). There were no differences between groups on the individual components myocardial infarction or all-cause mortality, although the study was not powered to detect a difference on these endpoints. FLORIDA 136 was a placebo-controlled trial of fluvastatin 80 mg in 540 patients with an acute myocardial infarction plus hypercholesterolemia and new or markedly increased chest pain or a new pathological Q wave. At 1 year of follow-up, there was no difference between groups in the occurrence of major coronary events. The A to Z trial 138 compared early intensive statin treatment (simvastatin 40 mg for 30 days and then simvastatin 80 mg thereafter) to a less aggressive strategy (placebo for 4 months and then simvastatin 20 mg thereafter) in patients with either non ST elevation acute coronary syndrome or ST elevation myocardial infarction with a total cholesterol level of 250 mg/dL or lower. Patients were followed for up to 24 months. Despite greater lowering of low-density lipoprotein in the early intensive group, there were no differences between the early intensive and less aggressive groups on the primary endpoint (cardiovascular death, myocardial infarction, readmission for acute coronary syndrome, or stroke), or on any individual component of the primary outcome. Nine patients in the simvastatin only group developed myopathy (creatine kinase level greater than 10 times the upper limit of normal with associated muscle symptoms) while taking 80 mg compared with 1 patient in the placebo first group (P=0.02). Three of the 9 in the simvastatin group had creatine kinase levels higher than 10 000 units/L and met the definition for rhabdomyolysis. The rate of myopathy was high, despite the exclusion of patients at increased risk of myopathy due to renal impairment or concomitant therapy with agents known to enhance Statins Page 51 of 128
Page 1 and 2: Drug Class Review HMG-CoA Reductase
Page 3 and 4: Final Report Update 5 Drug Effectiv
Page 49: Final Report Update 5 Drug Effectiv
Page 101 and 102:
Final Report Update 5 Drug Effectiv
Page 103 and 104:
Page 105 and 106:
Page 107 and 108:
Page 109 and 110:
Page 111 and 112:
Page 113 and 114:
Page 115 and 116:
Page 117 and 118:
Page 119 and 120:
Page 121 and 122:
Page 123 and 124:
Page 125 and 126:
Page 127 and 128:
Page 129 and 130:
Drug Class Review HMG-CoA Reductase
Page 131 and 132:
Page 133 and 134:
Page 135 and 136:
Page 137 and 138:
Page 139 and 140:
Page 141 and 142:
Page 143 and 144:
Page 145 and 146:
Page 147 and 148:
Page 149 and 150:
Page 151 and 152:
Page 153 and 154:
Page 155 and 156:
Page 157 and 158:
Page 159 and 160:
Page 161 and 162:
Page 163 and 164:
Page 165 and 166:
Page 167 and 168:
Page 169 and 170:
Page 171 and 172:
Page 173 and 174:
Page 175 and 176:
Page 177 and 178:
Page 179 and 180:
Page 181 and 182:
Page 183 and 184:
Page 185 and 186:
Page 187 and 188:
Page 189 and 190:
Page 191 and 192:
Page 193 and 194:
Page 195 and 196:
Page 197 and 198:
Page 199 and 200:
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
Page 207 and 208:
Page 209 and 210:
Page 211 and 212:
Page 213 and 214:
Page 215 and 216:
Page 217 and 218:
Page 219 and 220:
Page 221 and 222:
Page 223 and 224:
Page 225 and 226:
Page 227 and 228:
Page 229 and 230:
Page 231 and 232:
Page 233 and 234:
Page 235 and 236:
Page 237 and 238:
Page 239 and 240:
Page 241 and 242:
Page 243 and 244:
Page 245 and 246:
Page 247 and 248:
Page 249 and 250:
Page 251 and 252:
Page 253 and 254:
Page 255 and 256:
Page 257 and 258:
Page 259 and 260:
Page 261 and 262:
Page 263 and 264:
Page 265 and 266:
Page 267 and 268:
Page 269 and 270:
Page 271 and 272:
Page 273 and 274:
Page 275 and 276:
Page 277 and 278:
Page 279 and 280:
Page 281 and 282:
Page 283 and 284:
Page 285 and 286:
Page 287 and 288:
Page 289 and 290:
Page 291 and 292:
Page 293 and 294:
Page 295 and 296:
Page 297 and 298:
Page 299 and 300:
Page 301 and 302:
Page 303 and 304:
Page 305 and 306:
Page 307 and 308:
Page 309 and 310:
Page 311 and 312:
Page 313 and 314:
Page 315 and 316:
Page 317 and 318:
Page 319 and 320:
Page 321 and 322:
Page 323 and 324:
Page 325 and 326:
Page 327 and 328:
Page 329 and 330:
Page 331 and 332:
Page 333 and 334:
Page 335 and 336:
Page 337 and 338:
Page 339 and 340:
Page 341 and 342:
Page 343 and 344:
Page 345 and 346:
Page 347 and 348:
Page 349 and 350:
Page 351 and 352:
Page 353 and 354:
Page 355 and 356:
Page 357 and 358:
Page 359 and 360:
Page 361 and 362:
Page 363 and 364:
Page 365 and 366:
Page 367 and 368:
Page 369 and 370:
Page 371 and 372:
Page 373 and 374:
Page 375 and 376:
Page 377 and 378:
Page 379 and 380:
Page 381 and 382:
Page 383 and 384:
Page 385 and 386:
Page 387 and 388:
Page 389 and 390:
Page 391 and 392:
Page 393 and 394:
Page 395 and 396:
Page 397 and 398:
Page 399 and 400:
Page 401 and 402:
Page 403 and 404:
Page 405 and 406:
Page 407 and 408:
Page 409 and 410:
Page 411 and 412:
Page 413 and 414:
Page 415 and 416:
Page 417 and 418:
Page 419 and 420:
Page 421 and 422:
Page 423 and 424:
Page 425 and 426:
Page 427 and 428:
Page 429 and 430:
Page 431 and 432:
Page 433 and 434:
Page 435 and 436:
Page 437 and 438:
Page 439 and 440:
Page 441 and 442:
Page 443 and 444:
Page 445 and 446:
Page 447 and 448:
Page 449 and 450:
Page 451 and 452:
Page 453 and 454:
Page 455 and 456:
Page 457 and 458:
Page 459 and 460:
Page 461 and 462:
Page 463 and 464:
Page 465 and 466:
Page 467 and 468:
Page 469 and 470:
Page 471 and 472:
Page 473 and 474:
Page 475 and 476:
Page 477 and 478:
Page 479 and 480:
Page 481 and 482:
Page 483 and 484:
Page 485 and 486:
Page 487 and 488:
Page 489 and 490:
Page 491 and 492:
Page 493 and 494:
Page 495 and 496:
Page 497 and 498:
Page 499 and 500:
Page 501 and 502:
Page 503 and 504:
Page 505 and 506:
Page 507 and 508:
Page 509 and 510:
Page 511 and 512:
Page 513 and 514:
Page 515 and 516:
Page 517 and 518:
Page 519 and 520:
Page 521 and 522:
Page 523:
show all

(Statins) and Fixed-dose Combination Products Containing a Statin

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?